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  • Engineering General  (9.884)
  • Rat  (4.427)
  • 301
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 436 (1998), S. 712-716 
    ISSN: 1432-2013
    Schlagwort(e): Key words ATP ; Distal colon ; Exocrine secretion ; K+ secretion ; Luminal receptors ; P2Y2 receptor ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We have previously investigated, in studies of rat distal colonic mucosa, the effect of ATP added to the basolateral side on ion transport and [Ca2+]i. It was demonstrated that ATP acts via a P2Y1 receptor to increase [Ca2+]i and NaCl secretion. In the present study we investigated the effect of luminally added nucleotides (ATP, UTP) on transepithelial voltage (V te) and resistance (R te) in Ussing chamber experiments on rat distal colonic mucosa. Both nucleotides induced a rapid and transient (within 30 s) change of V te to lumen-positive values (resting V te: –2±1 mV; peak V te after 100 µmol/l ATP: +2.4±1.1 mV) and a decrease of R te from 89.9±10.3 to 83.8±9.1 Ωcm2 (n=10). Similar values were obtained with luminal UTP (n=15). The estimated EC50 values for both nucleotides were approximately 6 µmol/l. The ATP-induced V te effect was nearly completely sensitive to Ba2+. Addition of the K+ channel blocker Ba2+ (1 mmol/l) to the luminal solution reversibly inhibited 77±4% (n=5) of the ATP-induced V te effect. Experiments to identify the respective P2 receptor subtype revealed the following rank order of potency at 500 µmol/l agonist: UTP≥ATP〉〉2-methylthio-ATP=ADP〉〉adenosine〉 AMP〉β,γ-methylene-ATP (n=5). This closely resembles the published rank order for the P2Y2 receptor. Using the reverse-transcriptase polymerase chain reaction (RT-PCR) technique P2Y2 receptor-specific mRNA was detected in total RNA extracted from isolated crypts. In summary these data indicate that luminal ATP and UTP act via a P2Y2 receptor in the luminal membrane of colonic mucosa to elicit a transient K+ secretion.
    Materialart: Digitale Medien
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  • 302
    ISSN: 1438-2199
    Schlagwort(e): Basal ganglia ; Excitatory amino acids ; Monoamines ; Neuropeptides ; Microdialysis ; Immunocytochemistry ; Parkinson's disease ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary There is immunohistochemical evidence suggesting that glutamate (Glu) is released from nerve terminals and acts, via several receptor subtypes, as a major excitatory neurotransmitter in the cortico-striatal pathway of the rat. Aspartate (Asp) is also present in cortico-striatal neurons, but its role as a neurotransmitter has been questioned, since, in contrast to Glu, it has not been demonstrated in presynaptic vesicles. Glu and Asp can be found at subμM concentrations in the extracellular compartment of most areas of the basal ganglia. Their concentrations are largely regulated by transport mechanisms, but also by a synaptotagmin-dependent exocytotic release, and are sufficiently high to occupy junctional and extrajunctional receptors. We have investigated whether Glu and Asp release in the neostriatum can be selectively modulated by different neuronal systems. Dopamine (DA) and cholecystokinin (CCK) selectively stimulate Asp release, via D1 and CCKB receptor subtypes, respectively. Also opioid κ-agonists increase Asp release. We propose that the selective modulation of Asp release by D1−, CCKB- and κ agonists involves striatal neurons containing Asp, but not Glu. In contrast, local perfusion with the ,μ-opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-ThrPen-Thr-NH2 (CTOP) increases both Glu and Asp release. This effect is probably exerted on cortico-striatal terminals, via presynaptic inhibitory μ-receptors. Thus, these results demonstrate that extracellular levels of Glu and Asp are modulated differentially by different neuronal systems, and suggest that in the neostriatum of the rat there are neuronal populations using Glu and/or Asp as messenger(s).
    Materialart: Digitale Medien
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  • 303
    ISSN: 1432-2072
    Schlagwort(e): Key words Affect ; Aggression ; Antinociception ; Opioids ; Rat ; Stress ; Vocalization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The present experiments evaluated the influence of intraventricular μ and δ opioid receptors on affective vocal and reflexive responses to aversive stimuli in socially inexperienced, as well as defensive and submissive responses in defeated, adult male Long-Evans rats. Defeat stress consisted of: (1) an aggressive confrontation in which the experimental intruder rat exhibited escape, defensive and submissive behaviors [i.e., upright, supine postures and ultrasonic vocalizations (USV)], and subsequently, (2) protection from the resident stimulus rat with a wire mesh screen for 10–20 min. Defeat stress was immediately followed by an experimental session with tactile startle (20 psi). The μ opioid receptor agonists morphine (0.1–0.6 μg ICV) and [D-Ala2-N-Me-Phe4-Gly5-ol]-enkephalin (DAMGO; 0.01–0.3 μg ICV), and the δ opioid receptor agonist [D-Pen2,5]-enkephalin (DPDPE; 10–100 μg ICV) dose-dependently decreased startle-induced USV and increased tail-flick latencies in socially inexperienced and defeated rats. Of greater interest, morphine, DAMGO and DPDPE increased the occurrence of the submissive crouch posture, and defeated rats were more sensitive than socially inexperienced rats to the startle-induced USV-suppressive and antinociceptive effects of morphine and DPDPE. The antinociceptive effects of DAMGO were likewise obtained at lower doses in defeated rats. Finally, the USV-suppressive effects of morphine and DAMGO were reversed with the μ receptor antagonist naltrexone (0.1 mg/kg IP), but the USV-suppressive effects produced by DPDPE were not reversed with the δ receptor antagonist naltrindole (1 mg/kg IP). These results confirm μ, but not δ opioid receptor activation as significant in affective vocal, passive-submissive behavior, as well as reflexive antinociception. Furthermore, similar to previous studies with restraint and electric shock stress, the facilitation of μ opioid effects on vocal responses and antinociception is consistent with the proposal that defeat stress activated endogenous opioid mechanisms.
    Materialart: Digitale Medien
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  • 304
    ISSN: 1432-2072
    Schlagwort(e): Key words Autoshaping ; Delay-of-reward ; Impulsivity ; Ethanol ; Sensitivity ; Individual differences ; Drug abuse ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Autoshaping conditioned responses (CRs) are reflexive and targeted motor responses expressed as a result of experience with reward. To evaluate the hypothesis that autoshaping may be a form of impulsive responding, within-subjects correlations between performance on autoshaping and impulsivity tasks were assessed in 15 Long-Evans hooded rats. Autoshaping procedures [insertion of retractable lever conditioned stimulus (CS) followed by the response-independent delivery of food (US)] were followed by testing for impulsive-like responding in a two-choice lever-press operant delay-of-reward procedure (immediate small food reward versus delayed large food reward). Delay-of-reward functions revealed two distinct subject populations. Subjects in the Sensitive group (n=7) were more impulsive-like, increasing immediate reward choices at longer delays for large reward, while those in the Insensitive group (n=8) responded predominantly on only one lever. During the prior autoshaping phase, the Sensitive group had performed more autoshaping CRs, and correlations revealed that impulsive subjects acquired the autoshaping CR in fewer trials. In the Sensitive group, acute injections of ethanol (0, 0.25, 0.50, 1.00, 1.50 g/kg) given immediately before delay-of-reward sessions yielded an inverted U-shaped dose-response curve with increased impulsivity induced by the 0.25, 0.50, and 1.00 g/kg doses of ethanol, while choice strategy of the Insensitive group was not influenced by ethanol dose. Ethanol induced impulsive-like responding only in rats that were flexible in their response strategy (Sensitive group), and this group also performed more autoshaping CRs. Data support the hypothesis that autoshaping and impulsivity are linked.
    Materialart: Digitale Medien
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  • 305
    ISSN: 1432-2072
    Schlagwort(e): Key words Acoustic startle response ; Prepulse inhibition ; Schizophrenia ; Sensitisation ; Amphetamine ; Dopamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Male Sprague-Dawley rats were repeatedly treated with amphetamine (AMP, 1 mg/kg, SC) at 3- day intervals for 15 days and tested for prepulse inhibition of acoustic startle after each treatment. This treatment regimen induced sensitisation in the animals as evidenced by a progressive increase in the disruptive effect of AMP on prepulse inhibition. Persistent changes in brain function was indicated, since an increase in disruptive effect was observed in sensitised animals also after a 22-day-long drug- and test-free period. The development of sensitisation was blocked by pretreatment with haloperidol (HPD, 0.1 mg/kg, SC), which suggests that sensitisation to the disruptive effect of AMP was dependent on dopamine (DA) D2 receptor activation. Furthermore, the development of sensitisation was blocked by adrenalectomy, which suggests that sensitisation was dependent also on circulating adrenal hormones. Increased DA-ergic activity has been implicated in the pathophysiology of schizophrenia and AMP-induced sensitisation to the neuronal functions that modulate prepulse inhibition may be an experimental model to investigate this hypothesis.
    Materialart: Digitale Medien
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  • 306
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 136 (1998), S. 70-74 
    ISSN: 1432-2072
    Schlagwort(e): Key words Self-administration ; Stimulus control ; Incentive-motivation ; Stimulus compounding ; Cocaine ; Food ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In previous experiments, the compounding of two discriminative stimuli associated with the same reinforcer increased rats’ responding approximately three-fold, regardless of whether the reinforcer was food, water, cocaine, or shock-avoidance. Compounding a discriminative stimulus associated with food with one associated with water increased responding two-fold. In the present experiment, compounding a discriminative stimulus associated with food with one associated with cocaine increased responding two-fold. These results support the hypothesis that 1) the effects of stimuli associated with reinforcers from the same incentive class (appetitive or aversive) are mutually enhancing, and 2) the combined effects of stimuli associated with two different reinforcers from within the same class are not as strong as those of two stimuli associated with the same reinforcer. These results also suggest that discriminative stimuli associated with non-drug reinforcers may increase the motivation to self-administer cocaine when encountered in combination with drug-related stimuli.
    Materialart: Digitale Medien
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  • 307
    ISSN: 1432-2072
    Schlagwort(e): Key words Nicotine ; Self-administration ; Dose ; Contingency ; Yoking ; Feeding ; Rat ; Sprague-Dawley
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The studies presented here were designed to further clarify the nature of nicotine self-administration (SA) based on a limited access model in which rats are food restricted, receive operant training using food reinforcement, and are then tested in daily 1-h drug sessions. We examined the effects of dose, feeding schedule, and contingency of drug delivery on acquisition of nicotine SA. Two doses of nicotine bitartrate, 0.03 and 0.06 mg/kg per infusion (free base), supported the transition from food-reinforced to drug-reinforced responding, although the pattern of behavior differed between these doses. In contrast, 0.01 mg/kg per infusion failed to maintain nicotine SA. In a second study, animals were divided into three groups according to feeding schedule. Rats that were both weight restricted and food deprived showed the highest level of SA behavior, although neither food deprivation nor weight restriction was necessary to establish SA. In the third experiment, rats that were switched from food to nicotine as the response-dependent reinforcer maintained higher response rates throughout a 9-day period than animals switched to response-independent (i.e., yoked) nicotine which showed minimal responding after day 1. Furthermore, the differences between self-administering and yoked animals emerged during the first session, suggesting that nicotine may serve as a reinforcer during the first drug exposure in naive animals. These results indicate that acquisition of nicotine SA can be influenced by both dose of nicotine and feeding schedule and that, in animals previously trained on a food-reinforced operant, active lever pressing is maintained only when nicotine delivery is contingent upon responding.
    Materialart: Digitale Medien
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  • 308
    ISSN: 1432-2072
    Schlagwort(e): Key wordsNeuroleptics ; Antipsychotic drugs ; Thalamus ; Fos immunohistochemistry ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The thalamus has been proposed as a site which may be involved in the production of the syndrome of schizophrenia and the response of schizophrenic symptoms to treatment. These studies test whether, consistent with this hypothesis, the activation of thalamic nuclei is a shared property of neuroleptic antipsychotic drugs. Rats were given single doses of the typical high and low potency neuroleptics haloperidol (1 mg/kg) and chlorpromazine (20 mg/kg), the atypical neuroleptics thiroridazine (20 mg/kg) and clozapine (20 mg/kg), the specific dopamine antagonist raclopride (3 mg/kg), the mixed dopamine/serotonin antagonist risperidone (3 mg/kg) or drug-free vehicle. Increased expression of Fos-like protein was utilized as a marker of cellular activation. All drugs tested, including typical and atypical antipsychotic agents, led to similar effects on the midline thalamic paraventricular, centromedian and rhomboid nuclei and the nucleus reuniens. These results suggest that midline thalamic nuclei may participate in neural circuits mediating some of the shared effects of antipsychotic drugs.
    Materialart: Digitale Medien
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  • 309
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 136 (1998), S. 148-152 
    ISSN: 1432-2072
    Schlagwort(e): Key words Indian Ginkgo biloba (IGb) ; Ginkgolic acid conjugates ; EGb 761 ; Anxiety ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Ginkgolic acid conjugates (GAC) (6-alkylsalicylates, namely n-tridecyl-, n-pentadecyl-, n-hepta- decyl-, n-pentadecenyl- and n-heptadecenylsalicylates) isolated from the leaves of Indian Ginkgo biloba Linn., (IGb) were tested for their putative role in anxiety in rats. Elevated plus maze, open-field behaviour, novelty-induced feeding latency and social interaction were the rodent behavioural models used in this study. GAC (0.3 and 0.6 mg/kg, each, PO) on single acute administration, showed dose-related changes in the behaviour. GAC (0.6 mg/kg) and DZ augmented open arm entries, the open arm/closed arm entries ratio and increased time spent in the open arm on the elevated plus maze. In the open field, GAC (0.6 mg/kg) and DZ significantly increased ambulation and reduced the immobility time. EGb 761 showed a similar profile. GAC (0.6 mg/kg) and DZ significantly attenuated the increased latency to feed in novel environment. By contrast, EGb 761 and Ginkocer further augmented feeding latency. None of the drugs tested showed any significant effect in the social interaction test. GAC showed consistent and significant anxiolytic activity in all the variables investigated. By contrast, EGb 761 and Ginkocer, which are devoid of GAC, did not evoke significant activity. However, increased rearing and decreased immobility time only in open field behaviour shown by EGb 761 may be due to some antianxiety activity of a lesser degree. Our observations suggest that GAC may be the active constituents of Ginkgo biloba responsible for the anxiolytic activity.
    Materialart: Digitale Medien
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  • 310
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 139 (1998), S. 95-107 
    ISSN: 1432-2072
    Schlagwort(e): Key words MK-801 ; Muscimol ; Discriminative stimulus ; Drug discrimination ; Ethanol ; GABAA ; NMDA ; Limbic system ; Nucleus accumbens ; Hippocampus ; Frontal cortex ; Amygdala ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  This study was conducted to assess the involvement of N-methyl-d-aspartate (NMDA) and γ-aminobutyric acid (GABA) receptor systems, located in specific limbic brain regions, in the discriminative stimulus effects of ethanol. Male Long-Evans rats were trained to discriminate between intraperitoneal (IP) injections of ethanol (1 g/kg) and saline on a two-lever drug discrimination task. The rats were then implanted with bilateral injector guides aimed at the nucleus accumbens core (AcbC), prelimbic cortex (PrLC), hippocampus area CA1 (CA1), or extended amygdala (i.e., at the border of the central and basolateral nuclei). Infusions of the non-competitive NMDA antagonist MK 801 in the AcbC or CA1 resulted in dose-dependent full substitution for IP ethanol. MK 801 infusion in the PrLC or amygdala failed to substitute for ethanol. Injection of the competitive NMDA antagonist CPP in the AcbC also failed to substitute for ethanol. Co-infusion of MK 801 in the hippocampus potentiated the effects of MK 801 in the AcbC, whereas NMDA infusion in the hippocampus attenuated the ability of MK 801 in the AcbC to substitute for ethanol. The direct GABAA agonist muscimol resulted in dose-dependent full substitution for IP ethanol when it was injected into the AcbC or amygdala, but failed to substitute when administered in the PrLC. Co-infusion of MK 801, but not CPP, potentiated the effects of muscimol in the AcbC. These results demonstrate that ethanol’s discriminative stimulus function is mediated centrally by NMDA and GABAA receptors located in specific limbic brain regions. The data also suggest that the discriminative stimulus effects of ethanol are mediated by interactions between ionotropic GABAA and NMDA receptors in the nucleus accumbens, and by interactions among brain regions.
    Materialart: Digitale Medien
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  • 311
    ISSN: 1432-2072
    Schlagwort(e): Key words Autoshaping ; Ethanol ; Pavlovian conditioning ; Lever-press ; Rat ; Learning ; Impulsivity ; Drug abuse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Approach responses, consummatory behaviors, and directed motor responses maintained by food reward resemble autoshaping CRs and are increased by lower doses of ethanol. This study evaluated the effects of presession IP injections of ethanol doses (0.00, 0.25, 0.50, 0.70, or 1.00 g/kg) on the acquisition of lever-press autoshaping CR performance in groups of male Long-Evans hooded rats. Paired groups received 15 daily sessions of Pavlovian autoshaping procedures, wherein the insertion of a retractable lever for 5 s (CS) was followed by the response-independent presentation of food (US). Ethanol facilitated lever-press autoshaping CR acquisition, as revealed by dose-related increases in the number of trials on which CRs were performed. The form of the dose-effect curve was inverted U-shaped with maximal responding induced during sessions 1–5 by the 0.70 g/kg ethanol dose. A similar dose-effect curve was observed during sessions 11–15, revealing that the effects of ethanol on autoshaping CR performance were relatively stable. A pseudoconditioning control group injected presession with 0.50 g/kg ethanol received training wherein the food US was presented randomly with respect to the lever CS. Few lever-presses were performed by the Random 0.50 group, indicating that ethanol’s effects on autoshaping CR acquisition and maintenance observed in the Paired 0.50 group were not due to its psychomotor activating effects. A non-injection control group performed more autoshaping CRs than did the control group injected presession with saline, indicating that daily presession IP injections per se suppress autoshaping CR performance. Results reveal that low doses of ethanol enhance Pavlovian conditioning of directed motor and consummatory-like responding maintained by food reward. Implications for autoshaping accounts of impulsivity and drug abuse are considered.
    Materialart: Digitale Medien
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  • 312
    ISSN: 1432-2072
    Schlagwort(e): Key words Isolation-rearing ; Ethanol ; Sucrose ; Saccharin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract These experiments examined the hypothesis that isolation-rearing and strain influence hedonic mechanisms. In experiment 1, voluntary consumption of ethanol and water was monitored in the home cage of Fawn Hooded (FH) and Wistar rats. FH rats were found to consume more ethanol at low concentrations than Wistar rats, independent of rearing condition, and isolation-reared rats were found to consume more of high ethanol concentrations, independent of strain. In experiment 2, isolation-reared rats were found to consume more sucrose, independent of concentration, than socially reared rats. In experiment 3, Fawn Hooded rats were found to be more sensitive to low concentration solutions of saccharin, and to consume less of the high concentration solutions, while isolation-rearing was found to enhance consumption of high concentrations. Thus, hedonic processes are independently modulated by strain and rearing conditions, although the effects of isolation-rearing appear to be exacerbated in Fawn Hooded rats.
    Materialart: Digitale Medien
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  • 313
    ISSN: 1432-2072
    Schlagwort(e): Key words Jaw-opening reflex ; α2-Adrenoceptor sensitivity ; Tail pinch ; Repeated stress ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract There are few in vivo studies which have investigated the modulation of central postsynaptic α 2-adrenoceptors functionality provoked by stress. We assessed in the rat the effects of either single or repeated tail pinch on clonidine-induced inhibition of the jaw-opening reflex (JOR) via activation of postsynaptic central α 2-adrenoceptors. At the end of each experimental period, the progressive inhibition of the digastric electromyographic responses elicited by orofacial electrical stimulation after the IV administration of cumulative doses (× 3.3) of clonidine (0.1–10 000 μg/kg) was recorded. Single tail pinch did not significantly modify the ability of the agonist to inhibit the JOR, although there was a tendency to decrease the basal amplitude of the reflex (a 40% reduction) immediately after exposure to the single stressor. However, the dose-response curve for clonidine-induced inhibition of the JOR was clearly shifted to the right in rats exposed to repeated tail pinch (ED50 was increased by 152%, P 〈 0.0001) when compared with the unstressed control group, without affecting the slope of the inhibitory function and the estimated maximum effect for the agonist. These results show that repeated stress leads to a subsensitivity of the α 2-adrenoceptors which modulate the JOR, suggesting the development of adaptive mechanisms in postsynaptic α 2-adrenoceptors in response to stress.
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  • 314
    ISSN: 1432-2072
    Schlagwort(e): Key words Clonidine ; ST-91 ; CNQX ; LC ; Amygdala ; Intracerebral infusion ; Withdrawal ; Naloxone ; Morphine ; Opioid ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Both the locus coeruleus (LC) and the amygdala have been implicated in aspects of opiate dependence and withdrawal. The LC is known to be one of the most sensitive sites for precipitating withdrawal behaviors after local opiate antagonist infusions in morphine-dependent subjects. The amygdala is also known to mediate antagonist-induced withdrawal behaviors and aversive motivational states. The goal of the present study was to evaluate directly the ability of noradrenergic agonists and glutamatergic antagonists to attenuate naloxone-precipitated withdrawal behaviors when infused into the LC or the central nucleus of the amygdala (CeA). The alpha-2-noradrenergic agonists clonidine or ST-91 were infused into the CeA to compare the effects of noradrenergic activation in the CeA to the attenuation of withdrawal previously observed in rats infused with clonidine into the LC, since the LC and CeA are known to contain co-localized opiate and noradrenergic receptors. The effects of microinfusions of the non-NMDA excitatory amino acid antagonist 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) were also infused into the LC and CeA since opiate withdrawal is associated with increased glutamatergic transmission. Intra-CeA clonidine or ST-91 (2.4 µg/0.5 µl or 1.0 µl) produced significant reductions primarily in the occurrence of irritability. Conversely, intra-CeA or intra-LC infusions of CNQX (2.5 µg/0.5 µl) significantly attenuated naloxone-precipitated withdrawal, an effect similar to the attenuation previously observed after intra-LC clonidine infusions. These data demonstrate the specific behavioral effects of altering glutamatergic and noradrenergic neurotransmission in the LC or CeA during naloxone-precipitated opiate withdrawal. Elucidation of the neuroanatomical circuitry involved in opiate withdrawal should increase our understanding of the neuroadaptations associated with drug dependence and subsequent withdrawal behavior.
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  • 315
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 138 (1998), S. 176-183 
    ISSN: 1432-2072
    Schlagwort(e): Key words Alcohol ; Antidepressant ; Circadian ; Clomipramine ; Neonatal ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Neonatal exposure to antidepressant monoamine re-uptake inhibitors produces a wide variety of effects on the behavior and physiology of adult rats which are consistent with features of clinical depression. Since depressed patients show characteristic alterations in circadian rhythmicity, our laboratory has examined free-running circadian drinking rhythms in this putative animal depression model. Previously, neonatal desipramine treatment was shown to lengthen free-running period, and increase circadian amplitude, spectral magnitude, and voluntary alcohol intake (10% ethanol v/v) of male rats. The purpose of the present study was to examine the effects of neonatal clomipramine treatment (25 or 30 mg/kg SC, postnatal days 8–21) on circadian drinking rhythms and alcohol intake of both male and female rats. In addition, effects of alcohol exposure on circadian rhythmicity were also examined. Contrary to expectations, free-running period of clomipramine-treated rats did not differ from saline-treated controls in either constant darkness (DD) or constant light (LL), but spectral magnitude was increased in clomipramine-treated males and females, and circadian amplitude was increased in clomipramine-treated females. Neonatal clomipramine also increased voluntary alcohol intake, and both clomipramine- and saline-treated groups displayed significant period-shortening during alcohol exposure. Taken together, these results suggest that alterations in the amplitude and coherence of circadian rhythmicity may be more consistent than alterations in free-running period in animal depression models, as has been suggested previously for depressed patients.
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  • 316
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 140 (1998), S. 510-518 
    ISSN: 1432-2072
    Schlagwort(e): Key words Animal model ; Addiction ; Loss of control ; Dependence ; Withdrawal ; d-Amphetamine ; Opiate ; Alcohol ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37 ± 0.02 mg/kg per day, subordinate rats: 0.57 ± 0.05 mg/kg per day) and environmental variables (group housing: 0.21 ± 0.02 mg/kg per day, single housing: 0.41 ± 0.03 mg/kg per day). Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9 ± 0.2 mg/kg per day in week 47), although the experimental conditions remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6 ± 0.6 mg/kg per day; age-matched controls: 0.37 ± 0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1 ± 0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42 ± 0.04 mg/kg per day). Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol and opiates.
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  • 317
    ISSN: 1432-2072
    Schlagwort(e): Key words Δ9-THC ; Cannabinoids ; (R)-methanandamide ; Anandamides ; Efficacy ; Drug discrimination ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The objective of this study was to examine if (R)-methanandamide, a metabolically stable chiral analog of the endogenous ligand anandamide, is a cannabimimetic with a lower efficacy than Δ9-THC. Employing a two-lever choice drug discrimination procedure, rats were trained to discriminate between 1.8, 3.0, or 5.6 mg/kg Δ9-tetrahydrocannabinol (Δ9-THC) and vehicle. Different training doses were used in order to create assays with different efficacy demands. Generalization tests with 18 mg/kg (R)-methanandamide yielded around 90% Δ9-THC responses in the two lower Δ9-THC training dose conditions. However, only around 60% Δ9-THC responses occurred in the 5.6 mg/kg Δ9-THC training dose condition in tests with 18 mg/kg (R)-methanandamide; a higher dose (30 mg/kg) produced even fewer Δ9-THC-appropriate responses in this group. Morphine did not substitute for Δ9-THC. In conclusion, the data with Δ9-THC and (R)-methanandamide indicate that cannabinoid agonists can have varying degrees of intrinsic activity at a receptor site, or may produce their behavioral actions through multiple mechanisms, or both.
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  • 318
    ISSN: 1432-5233
    Schlagwort(e): Key words GLP-1(7-36)amide ; Glucose transport ; Skeletal muscle ; Rat ; Extrapancreatic effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Glucagon-like peptide-1 binding sites have been reported in peripheral tissues including muscle. However, the potential extra-pancreatic effects of glucagon-like peptide-1(7-36)amide are controversial. To evaluate whether glucagon-like peptide-1(7-36)amide has any effects on skeletal muscle glucose transport, isolated rat soleus muscles were incubated in increasing concentrations of insulin (0–150 nmol/l) in the presence or absence of 1 nmol/l glucagon-like peptide-1(7-36)amide for 3 h. Subsequently glucose transport was measured as uptake of [3H]-O-methylglucose. It was found that glucagon-like peptide-(7-36)amide has a small but significant stimulating effect on skeletal muscle glucose transport independent of the insulin concentration (P〈0.01). However, because of the magnitude of the observed effect, the physiological importance of glucagon-like peptide-1 (7-36)amide on skeletal muscle glucose metabolism is questionable.
    Materialart: Digitale Medien
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  • 319
    ISSN: 1432-2277
    Schlagwort(e): Key words FTY720 ; tacrolimus ; heart transplantation ; Tacrolimus ; FTY720 ; heart transplantation ; Heart transplantation ; FTY720 ; tacrolimus ; Rat ; FTY720 ; heart transplantation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract FTY720 is a recently discovered compound that is derived from the fungus Isaria sinclairii. Using a DA donor-to-LEW recipient rat combination, we assessed the efficacy of peritransplant FTY720 alone or in combination with post-transplant tacrolimus on the survival of cardiac allografts. Peritransplant FTY720 given orally at a dose of 5 mg/kg on days –1 and 0 prolonged graft survival from 5 to 13 days (P 〈 0.05). Combining peritransplant FTY720 with post-transplant tacrolimus resulted in a further prolongation of allograft survival. The lymphocyte count in transplanted rats decreased within 24 h to 46.6 %. Analysis of lymphocyte subsets by FACS revealed that FTY720 affected the total population of CD3-bearing T cells while the ratio of CD4 to CD8 cells remained unchanged. Kidney and liver biochemistry remained elevated for 2 weeks. In conclusion, FTY720 is a powerful immunosuppressive agent when used as induction therapy and may have an additive effect – perhaps a synergistic one – with post-transplant tacrolimus.
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  • 320
    ISSN: 1432-2277
    Schlagwort(e): Key words Liver transplantation ; Chimerism ; Bone marrow transplantation ; Rat ; FK506
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In this study, we investigated whether establishment of chimerism in donor liver with recipient-type bone marrow cells (BMCs) prior to liver transplantation could prolong the liver allograft survival. Donor female ACI rats were inoculated with recipient-type BMCs of male LEW rats via the portal vein, with or without irradiation as cytoablation, followed by intramuscular administration of FK506 for 5 days. At 1–2 months later, livers were harvested and transplanted into naive female LEW rats. No immunosuppressants were used. Chimerism in donor rats was confirmed by primers specific for the sex determinant Y chromosome of rats. With livers from rats pretreated with recipient-type BMCs, survival of liver allografts was significantly extended, irrespective of irradiation. These results showed that modification of the donor liver by intraportal injection of recipient-type BMCs and concomitant administration of FK506 prior to liver transplantation prolonged liver allograft survival in rats.
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  • 321
    ISSN: 1432-0878
    Schlagwort(e): Key words N18-RE-105 cells ; Glutamate ; p53 ; Adriamycin ; Etoposide ; Differentiation ; SV40 large T antigen ; Mouse ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Process extension was induced in cells of the N18-RE-105 neuroblastoma-retinal hybrid line by toxic agents, including glutamate and the p53-inducing anticancer agents adriamycin and etoposide. Both adriamycin and glutamate activated p53 as measured by a plasmid transfection assay. It was therefore hypothesized that SV40 large T antigen, which binds p53, would interfere with cellular differentiation. To test this hypothesis, the temperature-sensitive form of SV40 large T was transduced into N18-RE-105 cells by retroviral infection. SV40 large T-infected cells became de-differentiated, grew in tightly-packed colonies, lost expression of neurofilament, and lost the ability to differentiate in response to glutamate and adriamycin. The de-differentiating effect of SV40 large T antigen may be due to binding and inactivation of cellular proteins, such as p53, p107, p130, p300, and retinoblastoma protein, which are important in cellular growth and differentiation. It is suggested that p53 may play a role in cellular differentiation, perhaps under unusual circumstances involving stress or cytotoxicity.
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  • 322
    ISSN: 1432-0878
    Schlagwort(e): Key words Elastin ; TGF-β1 ; Arteries ; In situ hybridization ; Immunohistochemistry ; Northern blot ; Ageing ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Several in vitro studies have previously demonstrated that the addition of TGF-β to aortic smooth muscle cells or skin fibroblasts stimulates elastin synthesis. It is not clear however whether, in vivo, TGF-β participates in the regulation of elastin synthesis, especially in physiological conditions. The aim of our study was to explore the localization of elastin mRNA and TGF-β1 in the rat thoracic aorta (an elastic artery) and caudal artery (a muscular artery). Elastin mRNA was localized by in situ hybridization and quantified using Northern blot analysis. TGF-β1 was detected using immunohistochemistry. The study was carried out as a function of age (rats of 3, 10, 20, and 30 months). We observed that TGF-β1 immunoreactivity is present predominantly, but not exclusively, at the sites of elastin synthesis as determined by elastin mRNA detection: in smooth muscle cells in the aorta and in endothelial cells in the caudal artery. The ability of exogenously added TGF-β1 (0.001–10 ng/ml) to modulate the steady-state levels of elastin mRNA in primary cultures of endothelial cells, smooth muscle cells, and fibroblasts isolated from the thoracic aorta was also studied. At the highest concentration used, elastin mRNA levels increased 5-fold in endothelial cells and 11-fold in smooth muscle cells. The demonstration that TGF-β1 immunoreactivity is present at the sites of elastin synthesis in the thoracic aorta and in the caudal artery and the observation that TGF-β1 induces an increase in elastin mRNA levels in cultured endothelial cells and smooth muscle cells suggest that TGF-β1 may be implicated, at least in part, in the physiological regulation of elastin gene expression.
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  • 323
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 291 (1998), S. 445-454 
    ISSN: 1432-0878
    Schlagwort(e): Key words Serum-free medium ; Survival ; Chondroitin sulfate ; Culture substratum ; Brain neuron ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  When cells dissociated from the neonatal rat brains are plated on a poly-lysine-coated surface in a serum-free medium, they display a strange morphology: a dark and extended cell body. Preincubation of the surface with fetal bovine serum was found to inhibit the appearance of this strange contraction of the basal cell sheets in a dose-dependent manner. This finding indicated the presence of a factor(s) in the serum, which might be an appropriate substratum for prolonged survival of brain neurons. In the current study, this factor was highly purified through DEAE ion-exchange chromatography followed by gel filtration. The factor was eluted from a Superose column at fractions corresponding to a molecular weight greater than 1000 kDa. By SDS-PAGE analysis, these fractions were found to contain a major band (≥1000 kDa) positive for alcian blue and few minor bands faintly stainable with Coomassie blue. The activity of the purified sample, inducing the morphological change in cells, was diminished by incubation with chondroitinase ABC. Neither heparitinase II, hyaluronidase, nor trypsin modified the activity. An authentic chondroitin sulfate (type B) mimicked the serum action on the morphology of brain cells in early stages of culture. Taking these findings together, it is suggested that the factor in serum beneficial for the attachment of brain cells is composed of a chondroitin sulfate with a Mr greater than 1000 kDa. Cortical cells dissociated from the neonatal rat brain attached well to the purified factor-coated surface and displayed a healthy morphology: an optically-reflective cell body with thick neurites for at least 3 days in the absence of serum.
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  • 324
    ISSN: 1432-0878
    Schlagwort(e): Key words Retina ; Rod bipolar cells ; Amacrine cells ; Protein kinase C ; Glutamic acid decarboxylase ; GABA ; Synaptic circuitry ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  The synaptic connectivity between rod bipolar cells and GABAergic neurons in the inner plexiform layer (IPL) of the rat retina was studied using two immunocytochemical markers. Rod bipolar cells were stained with an antibody specific for protein kinase C (PKC, α isoenzyme), and GABAergic neurons were stained with an antiserum specific for glutamic-acid decarboxylase (GAD). Some amacrine cells were also labeled with the anti-PKC antiserum. All PKC-labeled amacrine cells examined showed GABA immunoreactivity, indicating that PKC-labeled amacrine cells constitute a subpopulation of GABAergic amacrine cells in the rat retina. A total of 150 ribbon synapses established by rod bipolar cells were observed in the IPL. One member of the postsynaptic dyads was always an unlabeled AII amacrine cell process, and the other belonged to an amacrine-cell process showing GAD immunoreactivity. The majority (n=92) (61.3%) of these processes made reciprocal synapses back to the axon terminals of rod bipolar cells. In addition, 78 conventional synapses onto rod bipolar axons were observed, and among them 52 (66.7%) were GAD-immunoreactive. Thus GABA provides the major inhibitory input to rod bipolar cells.
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  • 325
    ISSN: 1432-0878
    Schlagwort(e): Key words PC12 ; hNT2 ; Neuroblastoma cell lines ; NGF ; Retinoic acid ; Rat ; Human cell lines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Neuroendocrine-specific protein (NSP) reticulons are expressed in neural and neuroendocrine tissues and cell cultures derived therefrom, while most other cell types lack NSP-reticulons. Three major subtypes have been identified so far, designated NSP-A, NSP-B, and NSP-C. We have investigated the correlation between the degree of neuronal differentiation, determined by morphological and biochemical criteria, and NSP-reticulon subtype expression. For this purpose, several human neuroblastoma cell lines, exhibiting different degrees of neuronal differentiation, were examined immuno(cyto) chemically. It became obvious that the expression of NSP-C, as detected by immunofluorescence microscopy and Western blotting, is most prominent in cell lines with a high degree of neuronal differentiation, such as LA-N-5. Such highly differentiated cells also express other neural and neuroendocrine markers, such as neural cell adhesion molecule (NCAM), neurofilament proteins, synaptophysin, and chromogranin. NSP-A was observed in all cell lines to a different extent. However, no clear correlation was observed with the degree of neuronal differentiation as defined by other neuronal and neuroendocrine markers or morphology. NSP-B could not be detected. The induction of neuronal differentiation with nerve growth factor, dbcAMP, and retinoic acid in the rat pheochromocytoma cell line PC12 and the human teratocarcinoma cell line hNT2, respectively, induced the expression of NSP-A and NSP-C in these cell lines parallel to the induction of neurofilament protein expression. It is concluded that NSP-C expression, in particular, is strongly correlated with neuronal differentiation.
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  • 326
    ISSN: 1432-0878
    Schlagwort(e): Key words Osteoclasts ; Osteoblasts ; Osteocytes ; Bone ; Substance P (SP) ; Neurokinin-1 receptor (NK1-R) ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Substance P (SP) is a neuropeptide that is released from axons of sensory neurons and causes signal transduction through the activation of the neurokinin-1 receptor (NK1-R). The present study demonstrates the distribution of SP-like-immunoreactive (SP-LI) axons and the localization of NK1-Rs in rat bone tissue using the avidin-biotin-peroxidase complex method. Axons with SP-LI were commonly found near the trabecular bone in the temporal bone marrow, but they were only sparsely distributed in the mandible, femur, and tibia. Immunoreactivity for NK1-Rs was found on the plasma membrane and in the cytoplasm of the osteoclasts. In the osteoblasts and osteocytes, a small number of weak, punctate immunoreactive products of NK1-Rs were distributed close to the plasma membrane. At the electron-microscopic level, immunoreactivity for NK1-R was distributed mainly in the whole cytoplasm, except for the clear zone of the osteoclasts, and in pit-like structures along the plasma membrane. The NK1-R-immunoreactive structures in the cytoplasm were divided into two types of organelles, consisting of vesicular and vacuolar structures (probably transport vesicles and early endosomes). In the osteoblasts and osteocytes, the number of NK1-R-positive vesicular structures was fewer than in the osteoclasts. These results thus suggest that SP secreted by the sensory axons could directly modulate bone metabolism via NK1-Rs.
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  • 327
    ISSN: 1432-0878
    Schlagwort(e): Key words Vinculin ; Talin ; Integrin ; Dystrophin ; Spectrin ; T-tubule ; Costamere ; Basal membrane ; Cardiac muscle cell ; Dilated cardiomyopathy ; Human ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The transverse tubule system of the cardiomyocyte remains undeformed despite the extreme forces it undergoes during the contraction-relaxation cycle, but the morphological basis for its stability remains unclear. Therefore, we have investigated the architecture and subcellular protein scaffold of the cardiac T-tubules and compared it with that of the costameres and of the free sarcolemma. Tissue samples from normal rat and monkey hearts, and left ventricular tissue from normal and cardiomyopathic human hearts obtained at transplantation surgery were investigated using immunocytochemistry and confocal microscopy and by electron microscopy. In addition, we used a re-differentiation model of isolated, cultured adult rat cardiomyocytes. The cell membrane of the cardiac T-tubules was found to contain the cell-matrix focal adhesion molecules (FAMs) vinculin, talin, the α5β1 integrin and the membrane-associated proteins (MAPs) dystrophin and spectrin. FAMs and MAPs were localized in the T-tubular membrane in a similar pattern: in longitudinally oriented myocytes as transverse punctate lines at the Z-level; in transversally cut myocytes a radial tubular network was found to extend throughout the interior of the cell. Immunolabeling for basement membrane components including collagen IV, fibronectin and laminin showed a colocalization with FAMs and MAPs parallel to the transverse T-tubules. The costameres of the sarcolemma showed a protein composition resembling that of the T-tubules but the intervening segments of free sarcolemma showed absence of FAMs and presence of MAPs. For the first time, we demonstrate the existence and protein composition of the T-tubular scaffold in the human heart. Furthermore, we show that cardiomyocytes from human failing hearts have less abundant but more dilated T-tubules than do experimental animals. These results indicate that the cardiac T-tubular system contains a subcellular scaffold closely resembling that of the costameres. It consists of FAMs, MAPs and basal lamina proteins that confer structural integrity to the cardiac T-tubular membrane during contraction/relaxation cycles.
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  • 328
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 292 (1998), S. 345-354 
    ISSN: 1432-0878
    Schlagwort(e): Key words Pancreas ; Stomach ; Duodenum ; Ribonuclease protection assay ; Immunocytochemistry ; Protease ; Rat ; (Sprague Dawley)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Prior studies have revealed the presence of chymotrypsinlike protease in peripheral organs, although no definitive evidence for the synthesis of this enzyme in tissue other than the pancreas is available. In an attempt to detect chymotrypsinogen mRNA in peripheral organs, a fragment of the pancreatic chymotrypsin mRNA from rat was amplified using PCR. The sequence was identified as a portion of the rat chymotrypsin B gene overlapping exon 5 through exon 7. It was subcloned into the pGEM-4Z vector and used as a template for the vitro transcription of an antisense riboprobe. Using ribonuclease protection and Northern blot analyses, chymotrypsin mRNA was detected in the rat pancreas, stomach, duodenum, ovary, and spleen. Monoclonal and polyclonal antisera against chymotrypsin detected chymotrypsinlike immunoreactivity in rat and human pancreas, rat stomach, duodenum and jejunum. Electrophoresis and immunoblotting revealed chymotrypsin-chymotrypsinogen bands (25–29 kDa) in the stomach and duodenum. Synthesis of a potent protease such as chymotrypsin in tissue other than pancreas is significant, suggesting a potential physiological and/or pathological role in these tissues.
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  • 329
    ISSN: 1432-0878
    Schlagwort(e): Key words Connexin ; Gap junctions ; Smooth muscle ; Intestinal pacemaker ; Confocal laser scanning microscope ; Dog ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Cellular networks of pacemaker activity in intestinal movements are still a matter of debate. Because gap-junctional intercellular communication in the intestinal wall may provide important clues for understanding regulatory mechanisms of intestinal movements, we have attempted to clarify the distribution patterns of three types of gap junction proteins. Using antibodies for connexin40, connexin43, connexin45, smooth muscle actin, and vimentin, immunocytochemical observations were made with the confocal laser scanning microscope on cryosections of fresh-frozen small intestine and colon of the dog and rat. Connexin 45 was localized along the deep muscular plexus of the small intestine in both dog and rat. Double labeling studies revealed that connexin45 overlapped with vimentin –, but not actin-positive areas, indicating the fibroblast-like nature of the cells, rather than their being smooth muscle-like. Connexin43 immunoreactivity appeared along the smooth muscle cell surface in the outer circular layer of the small intestine of both animals. Connexin 40 immunoreactivity was not observed in the muscle layer other than in the wall of large blood vessels. It is suggested that connexin45-expressing cells along the deep muscular plexus of dog and rat small intestine are likely to act as a constituent of a pacemaker system, which may include a conductive system, by forming a cellular network operating via specific types of gap junctions.
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  • 330
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 292 (1998), S. 613-617 
    ISSN: 1432-0878
    Schlagwort(e): Key words Sensory nerve endings ; Calretinin ; Laryngeal mucosa ; Immunohistochemistry ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The distribution of laminar nerve endings that contained immunoreactive calretinin was examined in the laryngeal mucosa of the adult rat. In whole-mount preparations, the immunoreactive laminar endings were distributed in the supraglottic region but not in the subglottic region. The laminar endings that arose from thick nerve fibers with or without swellings were identified as corpuscles with many variform terminal arborizations. They appeared to be located at the interface between the epithelium and the subepithelial connective tissue. The terminals were scattered under the basal lamina of the epithelium, and some of them were located within the epithelial layer. Immunoelectron microscopy revealed that both sub- and intraepithelial immunoreactive terminals that were filled with mitochondria were partly or totally ensheathed by Schwann cell processes. The denervation experiments, in which the superior laryngeal nerve was cut unilaterally or bilaterally, suggested that the laminar endings originate from the superior laryngeal nerve with strict ipsilateral innervation. The laminar endings might be associated with detection of changes in pressure in the laryngeal cavity or chemical stimuli.
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  • 331
    ISSN: 1432-0878
    Schlagwort(e): Key words Adhering junctions ; Desmosomes ; Endothelial junctions ; Plaque proteins ; Desmoplakin ; Cadherins ; Protein ZO-1 ; Rat ; cell culture
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Two major types of plaque-bearing adhering junctions are commonly distinguished: the actin microfilament-anchoring adhaerens junctions (AJs) and the desmosomes anchoring intermediate-sized filaments (IFs). Both types of junction usually possess the common plaque protein, plakoglobin, whereas the other plaque proteins and the transmembrane cadherins are mutually exclusive. For example, AJs contain E-, N-, or P-cadherin in combination with α- and β-catenin, vinculin and α-actinin, whereas in desmosomes, desmogleins and desmocollins are associated with desmoplakin and one or several of the plakophilins (PP1–3). Here we describe a novel type of adhering junction comprising proteins of both AJs and desmosomes and the tight junction (TJ) plaque protein, ZO-1, in a newly established, liver-derived tumorigenic rat cell line (RMEC-1). By immunofluorescence microscopy, cell-cell contacts are characterized by mostly continuous-appearing lines which are usually resolved by electron microscopy as extended arrays of closely spaced small plaque subunits. These plaque-covered regions are positive for plakoglobin, α- and β-catenin, the arm-repeat protein p120, vinculin, desmoplakin and protein ZO-1. They are positive for E-cadherin in cultures early on in passaging, but tend to turn negative for all known cadherins in densely grown cultures. On immunoblotting SDS-PAGE-separated proteins from dense-grown cell monolayers, “pan-cadherin” antibodies have reacted with a band at ∼140 kDa, identified as N-cadherin by peptide fingerprinting of the immunoprecipitated protein, which for reasons not yet clear is modified or masked in immunolocalization experiments. The exact histological derivation of RMEC-1 cells is not known. However, the observations of several endothelial markers and the fact that all cells are rich in IFs containing vimentin and/or desmin, while only subpopulations also reveal IFs containing CKs 8 and 18, is suggestive of a mesenchymal, probably endothelial origin. We discuss the molecular relationship of this novel type of extended junction with other types of adhering junctions.
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  • 332
    ISSN: 1432-0878
    Schlagwort(e): Key words Nerve growth factor ; Hypertension ; Contact inhibition ; Proliferation ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Elevated target-derived smooth muscle nerve growth factor (NGF) and resultant neurogenic plasticity are associated with both hypertension and hyperactive voiding in spontaneously hypertensive rats (SHRs: hypertensive, behaviorally hyperactive). In culture, vascular (VSMCs) and bladder (BSMCs) smooth muscle cells derived from SHRs secrete higher levels of NGF, proliferate more rapidly, and achieve higher density at confluence than do control Wistar-Kyoto (WKY) cells. To elucidate growth-related contributions to the elevated tissue NGF observed in SHRs, we examined vascular VSMC and BSMC NGF secretion in two inbred cell lines (WKHTs, hypertensive; WKHAs, hyperactive) derived from SHRs and WKYs to assess the phenotypic association of altered NGF metabolism with either hypertension or behavioral hyperactivity. Cell density, rather than growth rates, was the most important factor with respect to NGF secretion. VSMC density varied such that WKHT=SHR〉WKY= WKHA, higher VSMC density being associated with higher NGF output. However, in BSMC cultures, NGF output was the lowest in high density cell lines, with WKHT〉SHR〉WKY〉WKHA. SHR BSMCs had the second highest cell density and NGF secretion level. Elevated packing density, presumably because of a lack of contact inhibition, co-segregated with the hypertensive phenotype in both VSMCs and BSMCs. Thus, dysfunctional smooth muscle growth characteristics may contribute to the augmented vascular and bladder NGF content associated with high blood pressure and hyperactive voiding in SHRs.
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  • 333
    ISSN: 1432-0878
    Schlagwort(e): Key words Endothelial cells ; Alkaline phophatase ; Primary cultures ; Proliferation ; Gene expression ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Primary cultures of rat myocardial capillary endothelial cells were established and characterized. A range of typical endothelial cell-specific markers were retained in vitro. Cell kinetic studies in confluent endothelial-cell cultures in vitro revealed a roughly 50-fold increase in the proportion of cells in s-phase, indicating a very considerable shortening of cell turnover time, compared to in vivo conditions. Alkaline phosphatase enzyme activity and encoding mRNA are strongly expressed in myocardial capillary endothelial cells in vivo, but were not detectable in vitro. This was true in cell cultures from two strains of rat, which revealed significantly different enzyme expression levels in vivo. In co-cultures of pericytes and endothelial cells, positive ALP enzyme reaction was detected in pericytes, which in vivo show only very weak enzyme reactivity. Treatment of cell cultures with ≤10 M retinoic acid had no effect in pure endothelial cell cultures, but did increase ALP expression of pericytes in co-cultures. The observation of a loss of endothelial ALP expression in vitro supports other in vitro as well as our own in vivo observations, indicating a negative correlation of ALP expression and proliferative activity of endothelial cells.
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  • 334
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 291 (1998), S. 575-579 
    ISSN: 1432-0878
    Schlagwort(e): Key words Chromatoid body ; Polysomes ; RNA ; Spermatid ; Spermatogenesis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  A procedure for isolating the chromatoid body from the testis of 40-day-old rats was developed. Electron-microscopical analysis indicated that about 70% of the isolated organelles were chromatoid bodies, while the remaining structures corresponded to dense bodies and probably to satellites. Negative staining of the isolated organelles revealed the presence of polysome-like structures in about 20% of the chromatoid bodies suggesting that the polysomes were not due to contamination with cytoplasmic polysomes. Moreover, the presence of RNA in the stroma of the chromatoid body was confirmed by RNAse-gold staining. Preliminary electrophoretic analysis of the RNA extracted from the organelles revealed the presence of a complex population of RNAs including 5.8 and 5 S ribosomal RNAs but no tRNA.
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  • 335
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 292 (1998), S. 367-375 
    ISSN: 1432-0878
    Schlagwort(e): Key words Larynx ; Edema ; Mast cells ; Compound 48/80 ; Substance P ; Capsaicin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  In the rat larynx, plasma exudation and edema formation were studied by light and electron microscopy after i.v. injections of the mast cell activator compound 48/80, substance P, and capsaicin. The morphological effects of substance P and capsaicin on connective tissue mast cells in vivo were also examined. Of the drugs tested, only compound 48/80 degranulated the connective tissue mast cells. All drugs induced a subepithelial plasma exudation in the subglottic region, with edema in the lamina propria and widened intraepithelial intercellular spaces, though the tight junction regions seemed intact. In the epiglottis, 10 min after compound 48/80 injection, there was edema in the lamina propria on the lingual side, with an intact and tight epithelial lining. No morphological sign of edema was found in the epiglottis after injection of substance P or capsaicin. The pronounced effect found in the epiglottic region after compound 48/80 injection was due to the release of mediators such as histamine and 5-hydroxytryptamine from the connective tissue mast cells. This study supports the belief that substance P in vivo mediates an increased vascular permeability by a direct effect on the blood vessels – a mechanism distinct from mast cell degranulation.
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  • 336
    ISSN: 1432-0878
    Schlagwort(e): Key words Angiogenesis ; Capillary growth ; Prazosin ; Shear stress ; Skeletal muscle ; Ultrastructure ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Chronic vasodilatation represents a stimulus for capillary growth associated with increased luminal shear stress. We have examined the ultrastructure of more than 2000 capillaries to establish whether the sequence of angiogenesis in response to this stimulus is similar to that described during development and under pathological circumstances. Administration of the α1-blocker prazosin to rats for 2 weeks led to a greater capillary length density in extensor hallucis proprius muscles without any change in capillary tortuosity: J v(c,f)=262±54 compared with 350±17 mm–2, control compared with prazosin (P〈0.002). There were obvious signs of endothelial cell (EC) activation after prazosin treatment, including an increased proportion of capillaries with rough endoplasmic reticulum, large cytoplasmic vacuoles, thickened endothelium and an irregular luminal surface. Capillaries from control muscles had a maximum of three ECs in cross section, whereas four ECs were noted in 0.8+0.5% of capillaries after 1 week (n.s.) and 2.5±0.9% after 2 weeks (P〈0.01) of treatment. This could be due to elongation and/or migration of ECs, as cell proliferation has not been described at these time points. There was also an increase in the proportion of capillaries having a narrow, slit-like lumen (1.7±0.8% of controls; 7.1±1.9% at 1 week; 8.8±2.5% at 2 weeks; P〈0.02), some of which were smaller in size (less than 2 μm diameter) than in controls (3–5 μm) and/or “seamless”, i.e. lacking EC junctions. These may represent newly formed vessels. Focal discontinuity of the basement membrane and abluminal EC processes were rarely seen, and capillary growth by abluminal sprouting appeared to be very infrequent (less than 0.001% of profiles). Of more importance was growth starting from the luminal side. Significantly more thin cytoplasmic processes were observed protruding into the lumen of capillaries after 1 week (47.5±6.2%, P〈0.001) and 2 weeks of prazosin (34.2±5.5%, P〈0.05) than in control vessels (16.7±3.9%). Some of these traversed the entire lumen and connected with endothelium of the opposite side, probably involving membrane fusion, resulting in the appearance of a double lumen. Individual capillaries with a complete double lumen were observed after 2 weeks’ prazosin but comparatively rarely, in only four out of six muscles. These findings indicate a pattern of luminal growth which is completely different from intussusceptive growth previously described during development, and from the abluminal capillary sprouting seen under pathological circumstances.
    Materialart: Digitale Medien
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  • 337
    Digitale Medien
    Digitale Medien
    Springer
    Annals of biomedical engineering 26 (1998), S. 526-533 
    ISSN: 1573-9686
    Schlagwort(e): Rat ; Artery: femoral ; Arterial diameter ; Vasomotion ; Shear stress ; Flow-dependent constriction ; Step flow ; Oscillating flow
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Technik allgemein
    Notizen: Abstract The effects of flow and flow changes on arterial diameter were investigated in vitro on isolated rat femoral arteries. Segments of femoral arteries were excised, mounted on microcannulas, and perfused with Tyrode's solution (37°C). Perfusion pressure was kept constant at 90 mm Hg. The mean external diameter after equilibration at a transmural pressure of 90 mm Hg was 720 ± 50 μ m (n=12). Vessels were then constricted with norepinephrine (1 μM in the superfusion solution) to 77% ± 13% of the resting diameter; acetylcholine was used to check endothelial function. The external diameter was measured continuously using video microscopy. The arteries were subjected to two different types of flow variations: (a) step changes in flow (increase and decrease, n=6) and (b) low-frequency sinusoidal flow variations (frequencies ranging from 0.002 to 0.1 Hz, n=11). Flow ranged from 0 to 800 μ l/min (shear stress ranging from 0 to 15 dyn/cm2). All measured vessels constricted as flow increased. Flow steps induced exponential-like contractions (flow increase) or relaxations (flow decrease) with mean characteristic time constants 31 ± 4 and 22 ± 2 s, respectively. Sinusoidal flow oscillations induced sinusoidal diameter oscillations with a time delay. An increase in the frequency of the flow led to a decrease of both the amplitude of the flow-induced diameter oscillations and the phase shift between flow and diameter. The dynamic diameter response to flow changes could be characterized by a first-order low-pass filter with a time constant of 22 s. © 1998 Biomedical Engineering Society. PAC98: 8745Hw
    Materialart: Digitale Medien
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  • 338
    ISSN: 1435-0130
    Schlagwort(e): Key words Burn injury ; Stress protein ; Systemic organs ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We have previously reported that in severely burned rats, the induction of 72-kD stress protein (HSP72) increased in various systemic organs. In this present study, in order to compare the stress response of systemic organs to burn injury of a smaller total body surface area with those of an extensive burn, we investigated the induction of 72-kD heat shock protein (HSP72) in various organs (brain, hypophysis, lung, heart, liver, pancreas, spleen, kidney, adrenal gland, and skeletal muscle) of burned rats. A dermal burn was developed on the skin by immersing the rats in hot water (90° C) for three seconds. At 0, 24 and 48 h after burn injury, the HSP72 induction of various organs was examined by Western blot analysis. In the single hind leg burn, the level of HSP72 did not increase at any time in all ten organs. In the double hind leg burn, at 48 h, the induction of HSP72 increased more than 1.5 fold compared to the control in the hypophysis (1.6 fold) and the heart (1.8 fold). These results indicate that the double hind leg burn causes a stress response in the hypophysis and the heart, while the single hind leg burn does not cause this stress response. In extensively burned rats, the degree of the stress response of the systemic organs to the burn injury depends on the burn size, and the intensity of “burn stress” to the systemic organs in a double or single hind leg burn is relatively small compared with those in extensive burns at the molecular level.
    Materialart: Digitale Medien
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  • 339
    Digitale Medien
    Digitale Medien
    Springer
    Methods in cell science 20 (1998), S. 203-207 
    ISSN: 1573-0603
    Schlagwort(e): Endocarditis ; Rat ; Streptococci
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The rat model of endocarditis is a well established experimental protocol which closely approximates human native valve endocarditis. The rat model of endocarditis has been used to examine the role of particular streptococcal virulence factors, to assess immunoprotective strategies, and to evaluate the efficacy of selected antibiotic treatment regimens for streptococcal endocarditis. Like humans, rats are generally susceptible to endocarditis only if the cardiac valves have been damaged. In the rat model of endocarditis, damage to the aortic valve and sterile vegetation formation is accomplished by insertion of a polyethylene catheter through the carotid artery into the left ventricle. Following catheter insertion, an inoculum of streptococci are injected intravenously. Vegetations removed from the heart valves during thoracotomy of euthanized animals are qualitatively cultured for streptococcal infection. The method, including investigator safety considerations, is described in detail.
    Materialart: Digitale Medien
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  • 340
    Digitale Medien
    Digitale Medien
    Springer
    Plant foods for human nutrition 52 (1998), S. 97-108 
    ISSN: 1573-9104
    Schlagwort(e): Hypertriglyceridemia ; Protein ; Rat ; Retinoid ; Soy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Previous research carried out in an animal model of retinoid-induced hypertriglyceridemia – rats fet a 13-cis retinoic acid (13cRA)-containing diet having casein as the protein source – has demonstrated that the complete replacement of dietary casein with soy protein isolate (SPI) can decrease the severity of this condition. In this study, the effect of partially replacing dietary casein with SPI was investigated. Five groups of male Fischer 344 rats were used in a 14-day study, with two groups being fed diets having casein as the protein source, without or with 13cRA (groups A and B, respectively), and three groups being fed 13cRA-containing diets in which SPI was used to bring about the isonitrogenous replacement of 25, 50, or 100% of the casein in the formula for the diet used for group B (groups C-E, respectively). Serum triglyceride concentration for group B was significantly different ( p 〈 0.05) from that of groups A, D, and E (5.41 vs 2.62, 4.04, and 2.66 mmol/l, respectively). Serum cholesterol concentrations for groups D and E were significantly lower ( p 〈 0.05) than for groups A and B (1.63 and 1.60 vs 2.00 and 2.14 mmol/l, respectively). Thus, the isonitrogenous replacement of 50% of dietary casein with SPI can reduce the severity of retinoid-induced hypertriglyceridemia while decreasing the serum concentration of cholesterol.
    Materialart: Digitale Medien
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  • 341
    Digitale Medien
    Digitale Medien
    Springer
    Annals of biomedical engineering 26 (1998), S. 28-36 
    ISSN: 1573-9686
    Schlagwort(e): Mathematical model ; Tissue factor ; Wall shear rate ; FXa generation ; TF:FVIIa ; Rat ; Vascular ; Smooth muscle ; Factor X ; Coagulation ; Clot
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Technik allgemein
    Notizen: Abstract A computational model was developed to investigate the contribution of classical mass transport and flow parameters to factor X (FX) activation by the tissue factor–factor VIIa complex (TF:VIIa) on one wall of a parallel-plate flow chamber. The computational results were compared to previously obtained experimental data for the generation of factor Xa (FXa) by TF:VIIa on the surface of cultured rat vascular smooth muscle cells. In this study, the complete steady-state convection–diffusion equation was solved using the commercial software package, FLUENT (Fluent Inc., Lebanon, New Hampshire). A user-defined subroutine interfaced with FLUENT implemented the surface reaction which was modeled using classical Michaelis–Menten reaction kinetics. The numerical solutions were obtained for 12 cases which used combinations of three wall shear rates and four reaction rates. The numerically obtained fluxes for a given reaction rate displayed a wall shear rate dependence which ranged from classical kinetic reaction control (no dependence) to pure diffusional control (maximum dependence). The experimental data, however, were not represented by numerical data generated using a single reaction rate. The three numerically obtained fluxes which corresponded most closely to the experimental fluxes were determined using three different V max values. This finding supports the hypothesis that there may be a direct effect of flow on the TF:VIIa complex or the cell membrane. © 1998 Biomedical Engineering Society. PAC98: 8722-q, 8710+e
    Materialart: Digitale Medien
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  • 342
    ISSN: 1860-1499
    Schlagwort(e): Ischemia ; Delaved neuronal cell death ; Apoptosis ; Microglia ; Electron microscopy ; Rat ; Hippocampus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Morphological changes in the CA1 region of the hippocampus in the rat cardiac arrest model were studied with the in situ nick-end labeling (TUNEL) method and light and electron microscopy. The TUNEL-positive pyramidal cells first appeared on day 1, increased in number with time, and reached a peak at 7 days after recirculation. At the ultrastructural level, cell shrinkage, nuclear fragmentation, and an increased number of atuophagic vacuoles of the pyramidal cells were observed in the CA1 region. The brief ischemia activates the microglial cells in the CA1 region, and these cells were found to increase in number with time. The microglial cells were seen to adhere to degenerating pyramidal cells and to phagocytose the apoptotic neurons selectively.
    Materialart: Digitale Medien
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  • 343
    ISSN: 0173-0835
    Schlagwort(e): Rat ; Heart proteins ; Renovascular hypertension ; Two-dimensional polyacrylamide gel electrophoresis ; Computer-assisted gel analysis ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Hypertensive heart disease caused by renovascular hypertension reflects the response of the heart to an increased afterload and neurohormonal stimulation. We hypothesized that in this condition the composition of the myocardial proteins of rats was altered. To identify yet unknown quantitative and qualitative differences in myocardial proteins in renovascular hypertensive heart disease, we analyzed protein patterns by computer-assisted two-dimensional polyacrylamide large gel electrophoresis. Renovascular hypertension was induced by placing a silver clip on the left renal artery in 9-week-old rat siblings. Sham-operated animals served as controls. Systolic blood pressure (197 ± 19 mm Hg) and heart/body weight ratios (0.36 ± 0.04%) were significantly increased in the hypertensive animals. Twenty protein patterns from the left ventricle of five hypertensive and five control rats were compared. The molecular mass and isoelectric point (pI) of proteins spots ranging from 13 to 100 kDa and from 4.5 to 8.5, respectively, were determined using marker proteins. In total, 761 ± 88 protein spots were resolved in all twenty gels. For the quantitative data analysis a univariate (Mann-Whitney test) as well as a multi-variate statistical approach (correspondence analysis) were applied. Only one myocardial protein spot (molecular mass = 41.3 kDa; pI = 6.3) was decreased by more than twofold (p 〈 0.05) in renovascular hypertension. The vast majority of spots did not indicate a significant alteration of intensity. Left ventricular hypertrophy in early renovascular hypertension induces a form of myocardial hypertrophy that conserves the naturally occurring protein expression pattern.
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
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  • 344
    ISSN: 0173-0835
    Schlagwort(e): Cortex ; Cytoplasm ; Two-dimensional polyacrylamide gel electrophoresis ; Kidney ; Medulla ; Proteomics ; Rat ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: The rodent kidney is a target of many xenobiotics and is typified by regionally specific structure and function. This renders distinct regions of the kidney differentially susceptible to toxic exposure and effect. To characterize these differences at the proteome level, protein patterns from male rat kidney cortex and medulla cytosols were examined by two-dimensional electrophoresis (2-DE) and image analysis and prominent proteins identified immunologically or by matrix-assisted laser desorption/ionization - mass spectrometry (MALDI-MS) and electrospray/ionization - tandem mass spectrometry (ESI-MS/MS) sequence tag identification. An average of 727 protein spots were resolved and matched to the cortex cytosol reference pattern, and 716 in the medulla. Of this total, 127 proteins were found to differ in abundance (86 higher in cortex; 41 higher in medulla) (P 〈 0.001). Of those proteins that were detectable in both cortex and medulla, the abundance of 97 differed significantly while 30 proteins were found to be unique to one region or the other (26 in cortex, 4 in medulla). Twenty protein spots were identified and their regional differences are discussed. These results both confirm and expand our understanding of the molecular heterogeneity characterizing structurally and functionally distinct regions of the kidney and serve as a useful foundation for future nephrotoxicologic studies.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
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  • 345
    ISSN: 1530-0358
    Schlagwort(e): Rat ; Intraperitoneal ; 5-Fluorouracil ; Chlorhexidine ; Perforated colorectal cancer ; Recurrence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract PURPOSE: Colorectal cancer is a prevalent and mortal disease, resulting in nearly 55,000 deaths in the United States annually. Preoperative or intraoperative spillage of tumor cells because of perforation occurs in up to 10 percent of cases. When this spillage occurs, the chance of recurrence and death is dramatically increased. METHODS: In an effort to reduce the chance of recurrence and death, we used a rat model to evaluate the efficacies of intraperitoneal 5-fluorouracil and chlorhexidine in reducing the incidence of recurrence. Rats were injected with 10 mg/kg azoxymethane subcutaneously weekly for 12 weeks to induce colorectal cancers. At 20 weeks, subtotal colectomies were performed on rats with colorectal tumors and without peritoneal implants or liver metastases. At the time of surgery, a cut portion of the tumor was placed in the abdomen for 30 minutes; the rats then randomly received peritoneal irrigation with 5-fluorouracil, chlorhexidine, or sterile water (control). Eight weeks postoperatively a necropsy was performed. At that time, obvious and suspected recurrences and the anastomotic area were sampled for histologic evaluation. RESULTS: Significant differences were seen with chlorhexidine vs.water for gross tumor (P=0.05) and microscopic tumor (P 〈0.05). 5-Fluorouracil showed a greater rate of abscess formation vs.both control and chlorhexidine (P 〉0.05). CONCLUSIONS: Use of chlorhexidine intraperitoneal therapy at the time of the operation for perforated colorectal cancer significantly decreases the frequency of gross tumor recurrence but not total recurrences. Intraperitoneal 5-fluorouracil does not significantly decrease recurrence and may increase the risk of abscess when used intraoperatively.
    Materialart: Digitale Medien
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  • 346
    ISSN: 1435-1803
    Schlagwort(e): Rat ; collagen ; developed pressure ; pressure-volume relationships ; extracellular matrix
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Objectives: The impact of acute collagen disruption by the disulfide donor, 5,5′-dithio-2-nitrobenzoic acid (DTNB) on ventricular properties was tested in rat hearts.Methods: Collagen was degraded acutely in 13 isolated, isovlumically contracting rat hearts by perfusion with 1 mM DTNB added to Krebs-Henseleit solution for 1 hour followed by 2-hour perfusion with normal solution. Another 13 hearts were perfused with normal solution for 3 hours (Control).Results: Collagen content was 3.5±0.5% of ventricular dry weight in control group compared with 2.1±0.4% in DTNB group (decrease by 40%, p〈0.01). Scanning electron micrographs revealed loss of the delicate collagen network surrounding muscle fibers in DTNB treated hearts. Developed pressure at a fixed volume decreased to 86±17% of the baseline value after 3-hour perfusion in the control group, whereas in DTNB treated hearts developed pressure fell to 68±13% (p〈0.01). End-diastolic pressure was set at 5 mmHg at the beginning of the experiment and rose to 15±8 mmHg in control and 30±13 mmHg (p〈0.01) in the treated hearts. Concomitantly, wet-to-dry weight ratio increased from 5.63±0.26 in control to 6.07±0.11 (p〈0.05) in the DTNB treated hearts. A separate set of experiments on isolated myocytes excluded the possibility of a direct effect of DTNB on myocyte contractile function.Conclusions: These data suggested that with 40% collagen disruption by DTNB there is a significant increase in tissue edema that results in a decrease in chamber capacitance; in addition, there is a significant decrease in systolic performance which reflects the combined effect of edema and loss of collagen.
    Materialart: Digitale Medien
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  • 347
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 166-172 
    ISSN: 1432-1912
    Schlagwort(e): Key words Catalepsy ; VM nucleus ; Kainic lesions ; Pontine reticular formation ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Bilateral kainic acid lesions of the ventro-medial (VM) thalamic nucleus of rats which greatly reduced the catalepsy produced by haloperidol (2 mg/kg i.p.) not only did not reduce, but even enhanced, the cataleptogenic effect of eserine (1 mg/kg i.p.) and arecoline (30 mg/kg i.p.). This finding is in accord with former conclusions that catalepsy produced by cholinergic drugs does not depend on striatal mechanisms. In rats with kainic acid lesions of the VM thalamic nucleus, and similarly in intact, non-lesioned rats, systemic administration of eserine and arecoline potentiated the catalepsy produced by microinjections of carbachol (2 μg) into the pontine reticular formation (PRF). Atropine microinjected bilaterally into the PRF attenuated the cataleptogenic effect of eserine and arecoline i.p. We suggest that the PRF is a site at which systemically given cholinergic drugs act to produce catalepsy.
    Materialart: Digitale Medien
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  • 348
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 364-367 
    ISSN: 1432-1912
    Schlagwort(e): Key words Capsaicin ; CGRP (calcitonin ; gene-related peptide) ; Endothelium-dependent ; relaxation ; Thoracic aorta ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Previous studies have shown that pretreatment with calcitonin gene-related peptide (CGRP), a principal transmitter in sensory nerves, can protect the endothelial cell. We therefore evaluated whether in vivo capsaicin treatment prevents endothelial damage elicited by lysophosphatidylcholine (LPC) in the rat aorta. Acute treatment or repeated pretreatment with capsaicin resulted in stimulation of neurotransmitter release from sensory nerves or depletion of their transmitter content respectively. Vasodilator responses to acetylcholine (ACh) were examined in the aorta of these animals. Acute application of capsaicin (50 mg/kg) increased the plasma concentration of CGRP-like immunoreactivity (CGRP-LI) concomitantly with a reversal of the inhibition by LPC of endothelium-dependent ACh-induced relaxation in the isolated rat aorta. After repeated pretreatment with capsaicin to deplete sensory nerve neurotransmitter content the effects of capsaicin were absent as shown by the plasma CGRP-LI concentration and the vasodilator response to ACh. The results demonstrate that systemic capsaicin treatment, which evokes the release of CGRP from sensory nerves, protects the endothelial cell. The present study also suggests that CGRP may be an endogenous vascular protective substance.
    Materialart: Digitale Medien
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  • 349
    ISSN: 1432-1912
    Schlagwort(e): Key words Neuropeptide Y (NPY) ; Ca2+ efflux ; Y1 receptor ; Na+/Ca2+ exchange ; Na+ influx ; Cardiomyocyte ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Several physiological stimuli cause a rise in intracellular Ca2+ concentration ([Ca2+]i) in cardiomyocytes. This increased [Ca2+]i must be restored to physiological resting level to ensure response to further stimuli. In the present study, we examined the effect of neuropeptide Y (NPY), which is secreted from certain adrenergic or non-adrenergic neurons, on Ca2+ efflux from freshly isolated, quiescent adult rat cardiomyocytes. The isolated cardiomyocytes were preloaded with 45CaCl2 for 1 h. Then, the fractional release of 45Ca2+ from the cells was measured. NPY stimulated the efflux of 45Ca2+ from isolated adult rat cardiomyocytes in a concentration-dependent manner (10–8 M to 10–6 M). NPY (10–6 M)-induced Ca2+ efflux was 2.0 ± 0.16% of the total cellular content. The 45Ca2+ efflux from the cells was also stimulated by Y1 receptor agonist, [Leu31, Pro34]NPY, but not by Y2 receptor agonist, NPY13–36. The effect of NPY was inhibited by a peptide NPY inhibitor, NPY18–36 and a non-peptide NPY inhibitor, benextramine to a similar extent. From these results, it is conceivable that the effect of NPY on Ca2+ efflux from cardiomyocytes is mediated through Y1 receptors. It was also observed that NPY caused a rise in [Ca2+]i to almost 150 nM. NPY-stimulated 45Ca2+ efflux was not affected by removal of extracellular Ca2+, but was dependent on the presence of extracellular Na+. Moreover, NPY caused a 22Na+ influx into the cells of about 1.6-fold over the basal value which was inhibited by amiloride and 5-(N,N-dimethyl)-amiloride, known Na+/Ca2+ exchange inhibitors. In addition, isoproterenol also caused 45Ca2+ efflux from the cells and which was enhanced by the addition of NPY. These results suggest that NPY stimulates extracellular Na+-dependent 45Ca2+ efflux from freshly isolated adult rat cardiomyocytes, probably through its stimulatory effect on plasma membrane Y1 receptors with which NPY may couple during Na+/Ca2+ exchange.
    Materialart: Digitale Medien
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  • 350
    ISSN: 1432-1912
    Schlagwort(e): Key words 5-Hydroxytryptamine ; 5-HT1A receptors ; Microdialysis ; Flesinoxan ; WAY 100635 ; 8-OH-DPAT ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The modulation of extracellular 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala (CeA) by 5-HT1A receptors was studied by intracerebral microdialysis in awake and freely moving rats. Local administration of 1 μM tetrodotoxin (TTX), 60 mM K+ and perfusion with Ca2+-free Ringer containing EGTA confirmed that the major part of dialysate 5-HT levels from the CeA is of neuronal origin. Administration of 300 nM of RU 24969, a 5-HT1B receptor agonist, through the probe into the CeA decreased dialysate 5-HT levels to 67.2% of the baseline value. Systemic administration of the 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan dose-dependently decreased 5-HT levels in the CeA. The effect of 0.3 mg/kg of flesinoxan could be completely antagonized by systemic administration of 0.05 mg/kg WAY 100635, a 5-HT1A receptor antagonist. WAY 100635 alone had only minimal effects at this dose. These data show that a major part of the extracellular 5-HT in the CeA stems from 5-HT neurons and that the amount of 5-HT released into this brain region can be modulated by 5-HT1A receptors.
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  • 351
    ISSN: 1432-0843
    Schlagwort(e): Key words Anthracyclines ; Daunorubicin ; Daunorubicinol ; Pharmacokinetics ; Rat ; Aging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Age-related differences in pharmacokinetics may be important in determining altered anthracycline cardiotoxicity in the senescent rat and also in older humans. This study examined the effect of aging on daunorubicin pharmacokinetics in the Fischer 344 rat. Daunorubicin 7.5 mg/kg was administered i.v. to 6-and 24-month-old male Fischer 344 rats and plasma and tissue sampling was performed over 168 h for assay of daunorubicin and daunorubicinol concentrations by high-performance liquid chromatography. Systemic clearance of daunorubicin was decreased in older compared to younger animals (56±4 versus 202±17 ml min-1 kg-1; P〈0.05). In addition, the area under the plasma daunorubicinol concentration/time curve was significantly increased in older rats. In the heart, the area under the concentration/time curve was significantly increased in senescence both in the case of daunorubicin (201±12 versus 86±4 μg h g-1; P〈0.05) and daunorubicinol (1347±118 versus 182±4 μg h g-1; P〈0.05). Furthermore, the peak mean concentrations of daunorubicin were increased in older compared to younger rats both in plasma (1078±82 versus 663±66 ng ml-1; P〈0.05) and in heart (27±1 versus 10±1 μg g-1; P〈0.05). This also was true for daunorubicinol in plasma (284±39 versus 168±27 ng ml-1; P〈0.05) and in myocardium (8.6±0.6 versus 2.4±0.2 μg g-1; P〈0.05). Following daunorubicin injection, the ratio of daunorubicinol to daunorubicin concentrations in tissues increased with time, particularly in plasma and heart in senescent rats. Thus, there are significant age-related changes in daunorubicin and daunorubicinol kinetics in the rat that could alter susceptibility to acute systemic toxicity and to chronic cardiotoxicity.
    Materialart: Digitale Medien
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  • 352
    ISSN: 1433-2981
    Schlagwort(e): Peripheral blood ; Progenitor cells ; Rat ; Stem cells
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The assay system for determination of haemopoietic progenitors in peripheral blood of rats is essen tial for potential studies on mobilisation and transplantation of circulating progenitor cells in a rat experimental model. This paper demonstrates the possibility of detection and quantification of pluripotent progenitors (Colony Forming Units-Spleen day 8-CFU-Sd8) and committed progenitors (Colony Forming Units Granulocyte Macrophage-CFU-GM and Burst Forming Units-Erythroid-BFU-E) in peripheral blood of rats in a steady state. For determination of CFU-Sd8 the ‘rat to mouse’ in vivo assay was used, and for committed progenitors in vitro assays on methylcellulose were employed. The CFU-Sd8 incidence ranged from 7.3 to 11.6/ml of rat blood, similar to that reported in literature for mice. The incidence of CFU-GM was found to be 59.7 ± 9.4/ml which is in the range of the literature data for mice, rabbits, dogs and humans. The incidence of BFU-E in rat peripheral blood was 4.3 ± 1/ml, which was relatively low, but could be also considered as comparable with some literature data for dogs and humans. The CFU-E were not detected by the technique used. These results confirmed the existence of circulatory blood pluripotent progenitors (CFU-Sd8) and committed (CFU-GM and BFU-E) progenitors in rat, as has been established for some other mammalian species.
    Materialart: Digitale Medien
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  • 353
    ISSN: 1434-0879
    Schlagwort(e): BBN ; Bladder tumor ; Rat ; Endoscopy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Recent advances in tumor carbohydrate biochemistry have demonstrated antitumor effects of locally administered GM3 ganglioside on mouse MBT-2 tumor. When intravesical therapy inN-butyl-N(4-hydroxybu-tyl)nitrosamine (BBN)-induced rat bladder tumor is attempted, it is essential to identify the tumor, to classify its size before therapy and to monitor the effect of the therapy. To establish a more reliable experimental therapeutic system, we assessed the development of BBN-induced rat bladder tumor by endoscopic observation. BBN-induced bladder tumors in rats were observed serially using a 4.2-F flexible fiberscope. The endoscopic findings were compared with the histopathological findings. Intravesical tumor growth varied greatly between individual rats. The smallest change detected by endoscopy was a small edematous lesion histologically proved to be papilloma. The largest nodular lesion was determined to be a papillary, transitional cell carcinoma. This noninvasive method makes the BBN rat experimental system more reliable by allowing confirmation of tumor formation and classification of the tumor volume prior to therapy.
    Materialart: Digitale Medien
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  • 354
    ISSN: 1434-0879
    Schlagwort(e): Renal cell carcinoma ; Renal tubular transport ; Renal cortical slices ; p-Aminohippurate ; Human ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In vitro accumulation ofp-aminohippurate (PAH) was investigated in “intact” human renal cortical slices of normal kidney tissue and in tissue slices of renal cell carcinoma (RCC). The technique used was established in preliminary experiments on rat kidney tissue slices. In principle, the accumulation capacity is comparable in renal tissue slices of both species (slice to medium accumulation ratios between 4 and 8). In man sex differences in accumulation capacity do not exist. But, as shown in detail for rats, accumulation capacity drops with age. Tissue slices of RCC are unable to accumulate PAH actively; slice to medium ratio reaches about 1 and indicates passive PAH uptake only. Surprisingly, in tumors of stage pTl PAH uptake is lowest, perhaps as a sign of PAH transport out of the cells. There is no difference between peripheral and central parts of RCC. Age and sex are without influence on PAH uptake in RCC tissue slices. Interestingly, the accumulation capacity of “intact” tissue of kidneys infested with RCC also depends on the severity of the tumor (stage, diameter), but not on grading and formation of metastases.
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  • 355
    Digitale Medien
    Digitale Medien
    Springer
    Urological research 25 (1997), S. 173-177 
    ISSN: 1434-0879
    Schlagwort(e): αB crystallin ; Heat shock protein ; Rat ; Kidney neoplasms
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The expression of two small stress proteins, αB crystallin and the 27-kDa heat shock protein (HSP27), was studied quantitatively and immunohistochemically in normal kidney and renal tumors in rats. Levels of αB crystallin in renal cell tumors tended to be higher than in normal kidney (P = 0.07), but with a wide range of values, whereas they were significantly lower in mesenchymal tumors (P 〈 0.0001). In contrast, HSP27 concentrations in both renal cell (mean ± SD: 1790 ± 940 ng/mg protein,n = 15) and mesenchymal (1260 ± 1080 ng/mg protein,n = 10) tumors were significantly higher than the normal kidney value (142 ± 30 ng/mg protein,n = 10,P 〈 0.0001). A positive correlation was found between αB crystallin and HSP27 levels limited to the renal cell tumor case (Pearson's correlation coefficient,r = 0.68,P 〈 0.01). Immunohistochemistry revealed the loops of Henle to be positive for αB crystallin, whereas HSP27 staining was positive in glomerular and interstitial vascular walls and epithelial cells of proximal and distal tubules. Positive immunostaining for αB crystallin was demonstrated in six of nine renal cell tumors (67%) studied and for HSP27 in all of the nine cases (100%).
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  • 356
    ISSN: 0942-0940
    Schlagwort(e): Rat ; brain injury ; diffuse injury ; free radicals ; lipid peroxidation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Free radicals are generated after head injury. These radicals rapidly react with polyunsaturated fatty acids in the cell membrane and cause membrane destruction. This process is called lipid per-oxidation. Malondialdehyde (MDA) is one of the end products of lipid peroxidation, and it is a frequently used indicator of lipid per-oxidation in biological tissues. Using a diffuse head injury animal model, we studied the time course of lipid peroxidation in different regions of injured rat brains. In the present study, the MDA levels were 36.7%, 41.8%, and 35.1% greater than sham at one hour after injury at the frontal, parietal, and brain stem, respectively (p〈0.0001). The MDA levels in these regions continued to increase and peaked a 4 hours after the injury. The levels slowly decreased, and by 24 hours, they were still significantly higher than the sham control's. The elevation of MDA levels was less in the striatum and the temporal regions at one hour. They were 16.9% and 13.3%, respectively (p〈0.002). The MDA levels in these two regions continued to increase even after 4 hours of injury, but the degree of elevation never exceeded 35%. The results demonstrate that there is an immediate, posttraumatic burst of MDA production, suggesting the formation of free radicals after diffuse head injury. Even though all the regions sampled show the same effect, certain regions are less affected by this diffuse head injury animal model.
    Materialart: Digitale Medien
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  • 357
    ISSN: 1432-0533
    Schlagwort(e): Key words Schwann cell ; Diabetic neuropathy ; Human ; Animal model ; Galactose ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Despite early descriptions of hypertrophic Schwann cells and onion-bulb formation in patients with diabetic neuropathy, clinical and experimental studies have emphasized axonal pathology. In recent years, the Schwann cell has been further implicated in diabetic neuropathy because it is the primary intrafascicular location for the first enzyme of the polyol pathway, aldose reductase, which appears to have a role in modulating a variety of complications of diabetes, including diabetic neuropathy. To further explore the role of polyol pathway flux in the pathogenesis of Schwann cell injury, ultrastructural abnormalities of Schwann cells in human diabetic neuropathy (HDN) were compared with those in experimental galactose neuropathy (EGN), a well-characterized model of hyperglycemia without hypoinsulinemia. Similar to previous studies of EGN, reactive, degenerative and proliferative changes of Schwann cells were observed after 2, 4 and 24 months of galactose intoxication. Reactive changes included accumulation of lipid droplets, π granules of Reich and glycogen granules, increased numbers of subplasmalemmal vesicles, cytoplasmic expansion, and capping. Degenerative changes included enlargement of mitochondria and effacement of cristae, and disintegration of both abaxonal and adaxonal cytosol and organelles. Both demyelination and onion-bulb formation were seen at all time points, although supernumerary Schwann cells and axonal degeneration were most numerous after 24 months of galactose feeding. In sural nerve biopsy samples from patients with diabetes and progressive worsening of neuropathy, ultrastructural abnormalities in Schwann cells encompassed the full range of reactive, degenerative and proliferative changes described in galactose-fed rats. The concordance of fine-structural observations in nerves from galactose-fed rats and these adult-onset diabetic patients emphasizes the role of flux through aldose reductase in the complex pathology of diabetic neuropathy and points to the utility of galactose intoxication in helping to understand this metabolic disorder.
    Materialart: Digitale Medien
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  • 358
    ISSN: 1432-0533
    Schlagwort(e): Key words Microwave irradiation ; Mobile telephony ; Blood-brain barrier ; Vasogenic edema ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We investigated the effects of global system for mobile communication (GSM) microwave exposure on the permeability of the blood-brain barrier using a calibrated microwave exposure system in the 900 MHz band. Rats were restrained in a carousel of circularly arranged plastic tubes and sham-exposed or microwave irradiated for a duration of 4 h at specific brain absorption rates (SAR) ranging from 0.3 to 7.5 W/kg. The extravasation of proteins was assessed either at the end of exposure or 7 days later in three to five coronal brain slices by immunohistochemical staining of serum albumin. As a positive control two rats were subjected to cold injury. In the brains of freely moving control rats (n = 20) only one spot of extravasated serum albumin could be detected in one animal. In the sham-exposed control group (n = 20) three animals exhibited a total of 4 extravasations. In animals irradiated for 4 h at SAR of 0.3, 1.5 and 7.5 W/kg (n = 20 in each group) five out of the ten animals of each group killed at the end of the exposure showed 7, 6 and 14 extravasations, respectively. In the ten animals of each group killed 7 days after exposure, the total number of extravasations was 2, 0 and 1, respectively. The increase in serum albumin extravasations after microwave exposure reached significance only in the group exposed to the highest SAR of 7.5 W/kg but not at the lower intensities. Histological injury was not observed in any of the examined brains. Compared to other pathological conditions with increased blood-brain barrier permeability such as cold injury, the here observed serum albumin extravasations are very modest and, moreover, reversible. Microwave exposure in the frequency and intensity range of mobile telephony is unlikely to produce pathologically significant changes of the blood-brain barrier permeability.
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  • 359
    ISSN: 1432-0533
    Schlagwort(e): Key words Traumatic brain injury ; Hypothermia ; Fluid percussion ; Rat ; Contusion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Early outcome measures of experimental traumatic brain injury (TBI) are useful for characterizing the traumatic severity as well as for clarifying the pathomechanisms underlying patterns of neuronal vulnerability. However, it is increasingly apparent that acute outcome measures may not always be accurate predictors of chronic outcome, particularly when assessing the efficacy of potential therapeutic regimens. This study examined the chronic histopathological outcome in rats 8 weeks following fluid-percussive TBI coupled with moderate post-traumatic brain hypothermia, a protocol that provides acute neuronal protection. Animals received a moderate parasagittal percussive head injury (2.01–2.38 atm) or sham procedure followed immediately by 3 h of brain hypothermia (30°C) or normothermia (37°C). Eight weeks following TBI, serial tissue sections were stained with hematoxylin and eosin or immunostained for glial fibrillary acidic protein. Tissue damage, gliosis and immunoreactive astrocytes were observed in the ipsilateral thalamus, hippocampus, and in the neocortex lateral to the injury site. Within the thalamus, focal necrosis was restricted to selective thalamic nuclei. Significant hippocampal cell loss was found in the ipsilateral dentate hilar region of both TBI groups. Quantitative volume measurements revealed significant decreases in cortical, thalamic and hippocampal volume ipsilateral to the impact in both TBI groups. Lateral ventricles were substantially enlarged in the TBI-normothermia group, an effect which was significantly attenuated by post-TBI hypothermia. The attenuation of lateral ventricular dilation by post-traumatic hypothermia is indicative of chronic neuroprotection in this TBI model. These data provide new information concerning the chronic histopathological consequence of experimental TBI and the relevance of this trauma model to chronic human head injury.
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  • 360
    ISSN: 1432-0533
    Schlagwort(e): Key words Intercellular adhesion molecule 1 ; Immunohistochemistry ; Rat ; Brain ; Trauma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A study was made on the expression of the intercellular adhesion molecule 1 (ICAM-1) in cerebral microvessels after cortical contusion trauma of the rat brain. The trauma was produced by a free-falling weight on the exposed dura of one fronto-parietal lobe. Immunohistochemistry was done on cryostat sections using a monoclonal antibody and the reaction product was visualized using the avidin-biotin-peroxidase complex method. Control and sham-operated rats showed immunostaining of some penetrating arteries of the cerebral cortex, the epithelial cells of the choroid plexus and occasional microvessels of the brain parenchyma. The same pattern of immunostaining was seen in rats that were subjected to trauma and killed after 30 min. All rats with contusion trauma that were allowed to survive for 6–72 h showed a substantial increase in the number of immunostained capillaries throughout the site of the lesion. The ipsilateral hippocampus showed a mild to moderate increase in the number of immunostained microvascular profiles. This phenomenon was also present in the lateral thalamus of some rats. The staining was seen as an uninterrupted line at the position of the endothelial cells, indicating an up-regulation of this adhesion molecule after brain trauma. Up-regulation of ICAM-1 is a well-known phenomenon in inflammatory and ischemic lesions of the brain but has not previously been described in detail in traumatic brain injury. ICAM-1 may be involved in the production of several post-traumatic events such as leukocyte adhesion, microcirculatory disturbances and edema formation.
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  • 361
    ISSN: 1432-0533
    Schlagwort(e): Key words Parkinson’s disease ; Neural transplantation ; Allogeneic ; Major histocompatibility complex antigens ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Neural transplantation, as a therapeutic approach to Parkinson’s disease, still requires allogeneic graft material and raises questions of immunosuppression and graft rejection. The present study investigated the time course of major histocompatibility complex (MHC) expression and astrocytic response in allogeneic dopaminergic grafts, comparing two different grafting protocols. Adult 6-hydroxydopamine-lesioned Lewis 1.W rats received intrastriatal cell suspension grafts from the ventral mesencephalon of DA rat fetuses, either as single 1-μl macrograft via metal cannula or as four micrografts of 250 nl/deposit via a glass capillary. No immunosuppression was administered. Immunohistochemistry was performed at 1, 3, 6, and 12 weeks after grafting, using antibodies against donor- and host-specific MHC class I and II antigen, glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH). Most animals showed good allograft survival up to 12 weeks after transplantation with no signs of rejection. Reinnervation of the lesioned striatum by TH-positive neurites was observed from 3–6 weeks on. Expression of donor-specific MHC class I was comparably low in both allogeneic grafting groups, while host MHC class I and II reaction as well as astrocytic response tended to be higher in the macrografted animals. Donor MHC class II was not observed at any time point. It is concluded that intraparenchymal allografts of fetal mesencephalic cell suspensions can survive well in the rat Parkinson model without immunosuppression for at least 12 weeks, and that the expression of moderate amounts of donor-specific MHC class I antigen does not suffice to initiate a rejection process. In addition, the microtransplantation approach may reduce the level of trauma and subsequent MHC and GFAP expression and may, thereby, minimize the risk of graft rejection.
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  • 362
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 196 (1997), S. 417-426 
    ISSN: 1432-0568
    Schlagwort(e): Key words Neuronal plasticity ; Fiber growth ; Regeneration ; Rat ; CNS myelin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  After lesions in the central nervous system (CNS), the affected nerve fibers usually cannot regenerate and reconnect to their original target cells. One important reason for this failure to regenerate is the presence of neurite growth inhibitory molecules in the myelin sheath of central nerve fibers. Despite the absence of regeneration fiber growth can occur after CNS lesions from intact nerve fibers unaffected by the lesion. These fibers can form new collaterals and sprout into the region denervated by the lesion, thereby increasing their terminal arbors in a process called collateral sprouting. A certain functional compensation for the nerve fibers lost by the lesion can be achieved by this mechanism. In the spinal cord, collateral sprouting is extensive after lesions in young postnatal animals and decreases with increasing age. In the spinal cord of adult animals, axon sprouting can be observed but is strongly restricted. The factors that determine the amount of sprouting found after lesions at different ages are still largely unknown. Recent evidence suggests that the myelin-associated neurite growth inhibitors that suppress regeneration also restrict collateral sprouting in the spinal cord. In addition, the expression of growth-associated molecules, in particular the growth-associated protein GAP-43, by the sprouting nerve fibers appears to be an important determinant of the sprouting response. The robustness of the sprouting response is thus likely to be controlled by intrinsic growth determinants of the sprouting neuron as well as by the growth promoting and growth inhibitory properties of the microenvironment of the sprouting fibers.
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  • 363
    ISSN: 1432-1106
    Schlagwort(e): Transplant ; Striatum ; Substantia nigra ; Patch-matrix ; Regeneration ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract When patients with Parkinson’s disease initially show symptoms, approximately 80–85% of their dopaminergic nerve fibers in the striatum have degenerated. It is thus of importance to develop strategies to try to rescue the remaining dopaminergic neurons and to stimulate them to induce sprouting. In this study the goal was to examine whether the different subgroups of dopaminergic neurons in the ventral mesencephalon projecting to the basal ganglia have different sprouting capacities when stimulated by the trophic effect of a fetal striatal graft. Lateral ganglionic eminence was implanted into the lateral ventricle, the midportion of dorsal striatum, globus pallidus, or ventral striatum. Solid tissue pieces from 13- to 15-mm fetuses were stereotactically implanted into adult female Sprague-Dawley rats. At postgrafting week 4 the animals were perfused and processed for tyrosine hydroxylase (TH) immunohistochemistry. Transplants placed in the lateral ventricle were TH-negative, except for two cases with TH-positive fibers where the ependymal layer was disrupted, thereby allowing direct contact between the graft and the adjacent host striatum. The transplants placed into dorsal striatum were innervated by small patches of dopaminergic nerve fibers. Areas between the TH-positive patchy structures remained TH-negative. In grafts placed into globus pallidus, both patchy structures and a less dense TH-positive nerve fiber network was noted. The TH-positive growth pattern in transplants placed in ventral striatum was also devided into patchy and widespread growth. Grafts placed in globus pallidus and ventral striatum revealed significantly larger areas of TH-positive innervation compared with that measured in grafts placed in dorsal striatum and the lateral ventricle. In conclusion, it is possible to induce sprouting of TH-immunoreactive nerve fibers from all areas examined. The most potent areas to initiate dopaminergic growth were the globus pallidus and ventral striatum, where both a patchy dense and a widespread, less dense growth was induced. Thus, if using a trophic stimulus to induce sprouting from remaining dopaminergic nerve fibers in Parkinson’s disease, the preferential target to induce sprouting would be ventromedial striatum and growth would be guided toward dorsal striatum owing to the enhanced dopaminergic growth properties in the ventromedial areas.
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  • 364
    ISSN: 1432-1106
    Schlagwort(e): GABA ; Double immunostaining ; Retrograde tracing ; Diagonal band ; Disinhibition ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the septal complex, both parvalbumin and calbindin neurons cocontain GABA. In the same area, a large number of GABA-GABA synaptic connections can be observed. In order to further characterize their neurochemical nature, as well as the extrinsic and/or intrinsic origin of these GABA terminals, the following experiments were performed: (1) correlated light- and electronmicroscopic double immunostaining for calbindin and parvalbumin on septal sections of control rats; (2) light microscopic parvalbumin immunostaining of septal sections after surgical isolation (5 days) of the septum from its telencephalic or (3) hypothalamic afferents; and (4) parvalbumin immunostaining of sections prepared from the entire brain 2 days following horseradish peroxidase injection into the border between the lateral and medial septum. The results demonstrated that: (1) in a well-circumscribed, vertically longitudinal area located between the lateral and medial septum, 0.1–0.6 mm anterior to the bregma, a group of calbindin-containing, nonsomatospiny neurons are surrounded by parvalbumin-immunoreactive baskets; (2) these basket-forming axon terminals establish symmetric synaptic contacts with their targets; and (3) their cells of origin are not in the medial septum, but in the angular porition of the vertical limb. These observations indicate that a portion of the septal complex GABA-GABA synaptic connections represent functional interaction between two different types of GABAergic neurons. The presynaptic GABAergic neurons contain parvalbumin, and the postsynaptic GABAergic cells are immunoreactive for calbindin. Furthermore, a population of the medial septum/diagonal band parvalbumin neurons promect only to the hippocampus, while others, which may also send axons to the hippocampus, terminate on lateral septum calbindin cells as well.
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  • 365
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 113 (1997), S. 303-310 
    ISSN: 1432-1106
    Schlagwort(e): Hippocampus ; Adenosine A1 receptor ; DPCPX ; Purines ; Membrane partitioning ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Despite its potent proconvulsant effects in vitro, the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) does not induce seizures when administered in vivo. This contrasts with the effects of less selective adenosine antagonists such as theophylline or cyclopentlytheophylline, and led us to reexamine the nature of DPCPX-induced epileptiform activity. In the present study, we report that proconvulsant effects of bath-applied DPCPX in rat hippocampal slices are only observed after a preceding stimulus such as NMDA receptor activation or brief tetanic stimulation. While this may be due to the absence of a basal “purinergic tone”, the relatively high interstitial concentrations of adenosine present in the slice suggest that access of the drug to A1 receptors may instead be prevented by tightly coupled endogenous adenosine, with the ternary adenosine-A1 receptor-G protein complex stabilised in the high-affinity conformation by a coupling cofactor. This implies that a substantial percentage of adenosine A1 receptors are inactive under physiological conditions, but that access of adenosine A1 receptor antagonists may be facilitated under pathological conditions. Once induced, DPCPX-evoked spiking persists for long periods of time. A “kindling” effect of A1 receptor blockade is unlikely, since persistent spiking is not usually observed with less selective A1 antagonists even after prolonged application. Alternatively, endogenous adenosine released during increased neuronal activity may activate A2 receptors during selective A1 blockade. The most important factor determining the duration of DPCPX-induced spiking, however, may be a persistence of the drug in the tissue and subsequent access to the A1 receptor via a membrane-delineated pathway, since DPCPX-induced spiking could be shown to decrease markedly after a transient superfusion of theophylline. This hypothesis, which implies that the apparent affinity of adenosine antagonists for the A1 receptor is in part a function of their membrane partitioning coefficient, is supported by a close correlation between alkylxanthine logP values obtained from the literature and theirK i value at A1 receptors, but not at the enzyme phosphodiesterase, whose xanthine binding site is presented to the cytosol. The implications for the therapeutic value of purinergic drugs are discussed.
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  • 366
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 113 (1997), S. 343-352 
    ISSN: 1432-1106
    Schlagwort(e): Memory ; Glutamate receptors ; GABA receptors ; Modulatory sites of NMDA receptors ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Effects of redox reagents on excitatory and inhibitory synaptic responses as well as on the bidirectional plasticity of α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) andN-methyl-d-aspartate (NMDA) receptor-mediated synaptic responses were studied in CA1 pyramidal neurons in rat hippocampal slices. The oxidizing agent 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB, 200 μM) did not affect AMPA, GABAA or GABAB receptor-mediated synaptic responses or the activation of presynaptic metabotropic receptors. However, DTNB irreversibly decreased (by approximately 50%) currents evoked by focal application of NMDA. DTNB also decreased the NMDA component of the EPSC. The reversal potential of NMDA currents and the Mg2+ block were not modified. In the presence of physiological concentrations of Mg2+ (1.3 mM), DTNB did not affect the NMDA receptor-dependent induction of long-term potentiation (LTP) or long-term depression (LTD) expressed by AMPA receptors. In contrast, DTNB fully prevented LTP and LTD induced and expressed by NMDA receptors. Plasticity of NMDA receptor-mediated synaptic responses could be reinstated by the reducing agenttris-(2-carboxyethyl) phosphine (TCEP, 200 μM). These results suggest that persistent, bidirectional changes in synaptic currents mediated by NMDA receptors cannot be evoked when these receptors are in an oxidized state, whereas NMDA-dependent LTP and LTD are still expressed by AMPA receptors. Our observations raise the possibility of developing therapeutic agents that would prevent persistent excitotoxic enhancement of NMDA receptor-mediated events without blocking long-term modifications of AMPA receptor-mediated synaptic responses, thought to underlie memory processes.
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  • 367
    ISSN: 1432-1106
    Schlagwort(e): Key words Perinatal asphyxia ; Apoptosis ; Necrosis ; Hematoxylin-eosin ; DNA fragmentation ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The consequences of perinatal asphyxia on the rat brain were studied 80 min to 8 days after birth with hematoxylin-eosin and in situ DNA double-strand-breaks labeling histochemistry. Asphyxia was induced by immersing fetus-containing uterus horns, removed from ready-to-deliver Sprague-Dawley rats, in a water bath at 37°C for various time periods (0–22 min). Spontaneous- and cesarean-delivered pups were used as controls. Perinatal asphyxia led to a decrease in the rate of survival, depending upon the length of the insult. No gross morphological changes could be seen in the brain of either control or asphyctic pups at any of the studied time points after delivery. However, in all groups, nuclear chromatin fragmentation, corresponding to in situ detection of DNA fragmentation, was observed at different stages. Nuclear fragmentation in control pups showed a specific distribution that appeared to be related to brain maturation, thus indicating programmed cell death. A progressive and delayed increase in nuclear fragmentation was found in asphyctic pups, which was dependent upon the length of the perinatal insult. The most evident effect was seen in frontal cortex, striatum, and cerebellum at postnatal day 8, although changes were also found in ventral-posterior thalamus, at days 1 and 2. Thus, nuclear chromatin fragmentation in asphyctic pups indicates a delayed post-asphyctic neuronal death. The absence of signs of inflammation or necrosis suggests that delayed neuronal cell death following perinatal asphyxia is an active, apoptosis-like phenomenon.
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  • 368
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 247-256 
    ISSN: 1432-1106
    Schlagwort(e): Key words Entorhinal cortex ; Subiculum ; Retrohippocampus ; Latent inhibition ; Partial reinforcement extinction effect ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Experiment 1 assessed the effect of cytotoxic retrohippocampal (entorhinal and extra-subicular cortices) lesions on the development of latent inhibition (LI) using an off-the-baseline, between-subjects, conditioned emotional response paradigm. Sham-operated controls and unoperated rats that had been pre-exposed to a light stimulus prior to light-shock pairings showed less conditioned suppression towards the light stimulus than the nonpre-exposed animals, thus demonstrating LI. However, LI was not evident in rats with retrohippocampal lesions. In experiment 2, the same animals were trained to run in an straight runway for food. Half of the animals were trained under a 50% partial reinforcement schedule (i.e. they were rewarded randomly on half of the acquisition trials) and the other half were trained under a continuous reinforcement schedule (i.e. they were rewarded on every acquisition trial). When tested in extinction, animals trained on the partial reinforcement schedule showed greater persistence than animals trained on continuous reinforcement, thus demonstrating the partial reinforcement extinction effect (PREE). Rats with retrohippocampal lesions showed a PREE that was at least as clear as that seen in the sham-operated controls and in the unoperated animals. It is concluded that cytotoxic lesions of the retrohippocampal region selectively led to an abolition of LI, but spared the PREE. The present study thus provided evidence against the hypothesis that LI and the PREE share a common neural substrate.
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  • 369
    ISSN: 1432-1106
    Schlagwort(e): Key words Species differences ; CA2 ; Retrograde tracing ; Colocalization ; Theta rhythm ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Our recent studies showed the co-existence of substance P and calretinin in the supramammillo-hippocampal pathway of monkeys, as well as species differences in the synaptic targets of extrinsic substance P fibers in the hippocampi of monkeys and rats. Experiments used: (1) single and multiple stereotaxic injection of wheat germ agglutinin-conjugated HRP into the hippocampus and immunostaining for substance P in the supramammillary area; (2) colocalization of substance P and calretinin in supramammillary area cells; and (3) colocalization of these two neurochemicals in retrogradely labeled supramammillary projective cells of both male and female rats. These demonstrated: (a) many calretinin- and fewer substance P-immunoreactive neurons retrogradely labeled in the ipsilateral supramammillary area; (b) approximately 74% of all substance P cells contain calretinin and 9% of the calretinin neurons co-contain substance P; and, most importantly (c) none of the retrogradely labeled supramammillary cells colocalize calretinin and substance P. These results indicate the presence of two distinct supramammillo-hippocampal projections in the rat, one that contains substance P and the other calretinin. The latter innervates the same areas as those in the monkey, and the former terminates only in the CA2 hippocampal subfield.
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  • 370
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 129-136 
    ISSN: 1432-1106
    Schlagwort(e): Key words Fos-like immunoreactivity ; Middle cerebral artery ; Focal cerebral ischaemia ; Spinal cord neurons ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  This study examined c-fos protein expression in the brain and spinal cord of rats following permanent occlusion of the middle cerebral artery (MCA) above the rhinal fissure. At 1 h after right-sided MCA occlusion, Fos-like immunoreactivity (Fos-LI) was detected in neurons not only in the ipsilateral cerebral cortex but also in the spinal cord. In the latter, Fos-LI was localized in the nucleus and perikarya of neurons in the grey matter, notably the large motor neurons in the ventral horn. Fos-LI was most intense at 2–4 h, but became undetectable after 48 h in the cerebral cortex and 72 h in the spinal cord. In sham-operated animals, Fos-LI was almost undetectable or virtually absent. It was also not detected in the core territory supplied by the MCA at any time points after arterial occlusion. When the ischaemia-induced neuronal damage in both the cerebral cortex and spinal cord was evaluated by Nissl staining, some neurons appeared atrophic. We conclude that the induction of Fos-LI in neurons of the cerebral cortex and spinal cord is linked respectively to early onset–short stimulation and persistent excitatory or disinhibition phenomenon as a result of focal ischaemic brain injury.
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  • 371
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 113 (1997), S. 138-143 
    ISSN: 1432-1106
    Schlagwort(e): Parkinson’s disease ; Neural transplantation ; Cell death ; Lazaroid ; Dopamine ; Free radicals ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We explored the effects of congeners of nitrogen monoxide (NO) on cultured mesencephalic neurons. Sodium nitroprusside (SNP) was used as a donor of NO, the congeners of which have been found to exert either neurotoxic or neuroprotive effects depending on the surrounding redox milieu. In contrast to a previous report that suggests that the nitrosonium ion (NO+) is neuroprotective to cultured cortical neurons, we found that the nitrosonium ion reduces the survival of cultured dopamine neurons to 32% of control. There was a trend for further impairment of dopamine neuron survival, to only 7% of untreated control, when the cultures were treated with SNP plus ascorbate, i.e. when the nitric oxide radical (NO) had presumably been formed. We also evaluated the effects of an inhibitor of lipid peroxidation, the lazaroid U-83836E, against SNP toxicity. U-83836E exerted marked neuroprotective effects in both insult models. More than twice as many dopamine neurons (75% of control) survival when the lazaroid was added to SNP-treated cultures and the survival was increased eight-fold (to 55% of control) when U-83836E was added to cultures treated with SNP plus ascorbate. We conclude that the congeners of NO released by SNP are toxic to mesencephalic neurons in vitro and that the lazaroid U-83836E significantly increases the survival of dopamine neurons in situations where congeners of NO are generated.
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  • 372
    ISSN: 1432-1106
    Schlagwort(e): Antidiuretic hormone ; Osmotic stimulus ; Anteroventral third ventricular region ; Prostaglandins ; Meclofenamate ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study explored the roles of prostaglandins in the anteroventral third ventricular region, a cerebral osmoreceptor site, in the osmoregulation mechanism of vasopressin release. We injected (1 μl) prostaglandin E2 (12.8 nmol) or meclofenamate (78.3 nmol), an inhibitor of prostaglandin biosynthesis, into the brain region or the lateral cerebral ventricle of conscious rats, examining their effects on plasma vasopressin and its controlling factors in the presence or absence of an osmotic stimulus. The injection of prostaglandin E2 into the anteroventral third ventricular region augmented plasma vasopressin and arterial pressure after 5 min and 15 min, without influencing plasma osmolality, sodium, potassium, or chloride. In contrast, intraventricular injection of prostaglandin E2 did not cause any significant effect on those variables. The i.v. infusion (0.1 ml·kg−1·min−1) of hypertonic saline (2.5 mol/l) enhanced plasma vasopressin after 15 min and 30 min; this was accompanied by increased plasma osmolality, sodium, and chloride, and by unaltered or elevated arterial pressure. Meclofenamate given into the anteroventral third ventricular region 30 min before starting the hypertonic saline infusion abolished the osmotic vasopressin response without significantly changing the responses of the other variables. Histological analysis showed that the injection sites of meclofenamate in these rats were close to those of prostaglandin E2 in the anteroventral third ventricular region and included the organum vasculosum of the lamina terminalis and the surrounding area, the medial preoptic area, and periventricular and median preoptic nuclei. When injection cannulae for meclofenamate deviated from those areas incidentally or when the drug was expressly administered into the cerebral ventricle, the osmotic vasopressin response was not inhibited. Plasma vasopressin and the other variables observed during the i.v. infusion of isotonic saline (0.15 mol/l) were not affected significantly by meclofenamate administration into the anteroventral third ventricular region or the cerebral ventricle. On the basis of these results, we concluded that prostaglandins synthesized in and/or near the anteroventral third ventricular region might contribute to the facilitation of vasopressin release in the hyperosmotic state.
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  • 373
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 114 (1997), S. 51-62 
    ISSN: 1432-1106
    Schlagwort(e): Key words Pupillary light reflex ; Pretectum ; Anterograde and retrograde tracing ; GABA immunohistochemistry ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The olivary pretectal nucleus is a primary visual centre, involved in the pupillary light reflex. In the present study an ultrastructural analysis was made of the olivary pretectal nucleus by means of separate, anterograde and retrograde tracing techniques and immunohistochemistry of gamma-aminobutyric acid. Large-projection neurons and two types of gamma-aminobutyric acid-immunoreactive (GABA-ir) neurons are observed in the olivary pretectal nucleus. The primary dendrites of the projection neurons have a dichotomous appearance, the secondary dendrites a multipolar appearance. At the ultrastructural level the projection neurons have well-developed Golgi fields, abundant rough endoplasmic reticulum and the nucleus is always heavily indented. Numerous small GABA-ir neurons and a few medium-sized GABA-ir neurons are found. The small GABA-ir neurons contain a few stacks of rough endoplasmic reticulum and the nucleus is oval-shaped. The medium-sized GABA-ir neurons have well-developed Golgi fields, a moderate number of rough endoplasmic reticulum stacks and an indented nucleus. GABA-positive dendritic profiles containing vesicles also are observed. In the neuropil of the olivary pretectal nucleus, retinal terminals are found that contain round clear vesicles and electron-lucent mitochondria. They make asymmetric synaptic contacts (Gray type I) with dendritic profiles and with profiles containing vesicles. Terminals originating from the contralateral olivary pretectal nucleus exhibit small, round clear vesicles, electron-dense mitochondria and make asymmetric synaptic contacts (Gray type I) mainly with dendritic profiles. Two types of GABA-ir terminals were found. One type is incorporated in glomerulus-like arrangements, whereas the other type is not. GABA-ir terminals contain pleomorphic vesicles, electron-dense mitochondria and make symmetric synaptic contacts (Gray type II). Retinal terminals, terminals originating from the contralateral olivary pretectal nucleus and GABA-ir terminals are organized in glomerulus-like structures, in which dendrites of the large projection neurons form the central elements. Triadic arrangements are observed in these structures; a retinal terminal contacts a dendrite and a GABA-ir terminal and the GABA-ir terminal also contacts the dendrite. The complexity of the synaptic organization and the abundancy of inhibitory elements in the olivary pretectal nucleus suggest that the olivary pretectal nucleus is strongly involved in processing visual information in the pupillary light reflex arc.
    Materialart: Digitale Medien
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  • 374
    ISSN: 1432-1106
    Schlagwort(e): Key words Fascia dentata ; Mossy cells ; Interneurons ; Lucifer yellow ; Phaseolus vulgaris leucoagglutinin ; Septohippocampal projection ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Mossy cells in the hilus of the rat dentate gyrus are the main cells of origin of the dentate commissural and associational projections. They project along the septotemporal axis of the dentate gyrus and may thus influence the hippocampal signal flow in a longitudinal direction. To analyze the septal innervation of these hilar neurons, anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHAL) was used in combination with intracellular labeling of mossy cells (Lucifer yellow). Anterogradely labeled septal fibers impinge on proximal and distal dendrites of hilar mossy cells but spare the cell body. In contrast, numerous aspiny hilar neurons, presumably GABAergic interneurons, receive a septal innervation on their somata and proximal primary dendrites. These data demonstrate that septal fibers show a specificity for the dendritic segments of hilar mossy cells. Since mossy cells project predominantly to adjacent hippocampal lamellae, the activity of adjacent portions of the dentate gyrus may be influenced by the septal input onto these neurons.
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  • 375
    ISSN: 1432-1106
    Schlagwort(e): Key words Anionic surfactants ; Sodium dodecyl sulphate ; Blood-brain barrier ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The blood-brain barrier (BBB) arises from epithelial-like tight junctions that virtually cement adjoining capillary endothelium together in the brain microvascolature. Several experimental manipulations have been shown able to increase the permeability of brain capillaries, by altering endothelial cell membrane integrity or activating specific biochemical pathways involved in regulation of BBB functionality. Because of its amphiphilic nature, sodium dodecyl sulphate (an anionic surfactant widely used as solubilizer or stabilizer in several pharmaceutical preparations; SDS) may enter into interactions with the major membrane components, which are lipids and proteins. The aim of the present study was to determine the effect of an intracarotid infusion of SDS (25, 50 and 100 µg/kg; infusion rate: 3 ml/min for 30 s) on the functionality of the BBB in the rat. An extensive, dose-dependent Evans blue extravasation was observed, in the ipsilateral brain hemisphere, 15 min following SDS infusion. These results were confirmed by the significant increase in [14C]α-aminoisobutyric acid ([14C]AIB) transport (evaluated by calculating a unidirectional transfer constant, K i, for the tracer from blood to brain) measured in several ipsilateral brain regions 2 min after SDS infusion; this SDS-elicited BBB opening to [14C]AIB proved to be reversible. Since the BBB is created by the plasma membrane and tight junctions of the endothelial cells, the change in BBB permeability caused by SDS might be explained as a nonspecific surfactant-membrane interaction. Furthermore, SDS might affect the functional characteristics of brain vascular endothelial cells by an interaction with specific BBB proteins and/or biochemical pathways. In conclusion, one can suggest that intracarotid infusion of SDS might provide a useful clinical approach for the intentional introduction of different substances into the brain. On the other hand, these findings should call attention to possible dangerous consequences of using SDS as solubilizer in drug excipients.
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  • 376
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 116 (1997), S. 97-103 
    ISSN: 1432-1106
    Schlagwort(e): Key words Chronic constriction injury ; Infraorbital nerve ; Painful trigeminal neuropathy ; Heat-hyperalgesia ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Secondary trigeminal neuralgia (STN) follows an injury to the trigeminal nerve or one of its branches. Although rare, this condition results in great suffering and it is notoriously difficult to treat. The experimental analysis of painful neuropathy due to damage to the innervation of the limbs (e.g., the sciatic nerve) has progressed rapidly in recent years, but very few reports have appeared concerning experimental neuropathy in the trigemenial region. We report here an experimental rat model of trigeminal neuropathic pain produced by a chronic constriction injury to the infraorbital nerve (CCI-ION), and on a method that detects heat-evoked pain-related behavior. Rats with the CCI-ION have clear signs of heat-hyperalgesia when stimulated on the snout (the vibrissal pad). The hyperalgesia is seen both ipsi- and contralateral to the side of nerve injury, but is significantly more severe ipsilaterally, and lasts about 12 days.
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  • 377
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 520-530 
    ISSN: 1432-1106
    Schlagwort(e): Key words Hippocampus ; Learning ; Memory ; Recovery ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The monosialoganglioside GM1 is a compound with neurotrophic properties found to foster functional recovery in various paradigms of brain damage. The present experiment examined whether systemic treatment with GM1 may facilitate behavioral recovery in rats with fimbria-fornix lesions and intrahippocampal grafts rich in cholinergic neurons. Among 68 Long-Evans female rats, 46 sustained a bilateral electrolytic lesion of the fimbria and the dorsal fornix and 22 were sham-operated. Fourteen days later, half the lesioned rats were subjected to intrahippocampal grafts of a fetal septal cell suspension. Starting a few hours after lesion surgery and over a 2-month period, half the rats of each surgical treatment group received a daily injection of GM1 (30 mg/kg i.p.), the other half being injected with saline as a control. All rats were subsequently tested for locomotor activity and radial maze learning. The lesions induced locomotor hyperactivity and impaired learning performances in both an uninterrupted and an interrupted radial maze testing procedure. In all rats with surviving grafts, the grafts had provided the hippocampus with a new and dense organotypic acetylcholinesterase-positive innervation pattern which did not differ between saline- and GM1-treated subjects. The scores/performances of the rats that had received only the grafts or only the GM1 treatment did not differ significantly from those of their respective lesion-only counterparts. However, in the radial-arm maze task, the grafted rats given GM1 showed improved learning performances as compared with their saline-treated counterparts: they used more efficient visit patterns under the uninterrupted testing conditions and made fewer errors under the interrupted ones. The results suggest that GM1 treatment or intrahippocampal grafts used separately do not attenuate the lesion-induced behavioral deficits measured in this experiment. However, when GM1 treatment and grafts are used conjointly, both may interact in a manner allowing part of these deficits to be attenuated.
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  • 378
    ISSN: 1432-1106
    Schlagwort(e): Key words Amino acid immunocytochemistry ; Axon collateralization ; Thalamus ; Fluorescent tracers ; Limbic system ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Small, stereotaxically guided injections of true blue (TB) were made into the retrosplenial granular cortex (RSg) and of diamidino yellow (DY) into the dorsal portion of the rostral pole of the thalamic reticular nucleus (TRN) in 16 adult rats to determine whether axons projecting from the anterior thalamic nuclear complex (ATN) to the TRN are branches of axons also projecting to the RSg. Following injections of the fluorescent dyes, serial coronal sections of the brain revealed single retrogradely labelled, and large numbers of double retrogradely labelled neuronal cell bodies in the ipsilateral anteroventral and anterodorsal nuclei and smaller numbers in the anteromedial nucleus of the ATN complex. In a se- cond series of six adult rats with similar double injections of TB and DY, two sections in three were immunoreacted, one with antiserum against glutamate and one with antiserum against aspartate, using indirect immunofluorescence with rhodamine to detect reactive cells. The great majority of both single and double retrogradely labelled cell bodies were also immunoreactive for aspartate or glutamate. In addition, a moderate to small number of non-immunolabelled neurons projecting to the TRN and/or to the RSg were also found in all three nuclei of the ATN complex. These results are compatible with the possibility that large numbers of neurons in the ATN send axonal branches to both the RSg and the TRN, and that many such neurons use glutamate and/or aspartate as transmitters. The findings also suggest that the projections from the ATN might be heterogeneous with respect to transmitter phenotype.
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  • 379
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 117 (1997), S. 324-340 
    ISSN: 1432-1106
    Schlagwort(e): Key words Trigeminal nerve ; Mechanoreceptors ; Cutaneous sensory nerve ending ; Perivascular innervation ; Vibrissae ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  It is well established that sensory perception becomes impaired with advancing age and that, in parallel, dystrophy and degeneration of axons occur in sensory pathways. In this study, the impact of aging was examined in the mystacial pad, which receives a large variety of sensory nerve endings organized in a highly predictable pattern. Mystacial pad specimens from aged (30 months old) and young adult (2–3 months old) female Sprague-Dawley rats were processed, in parallel, for immunohistochemical analyses with antibodies against human neuronal cytoplasmic protein (protein gene product 9.5), transmitter enzymes, and several neuropeptides. Several changes in cutaneous innervation including both degenerative and regenerative processes were evident in the aged rat: (1) the Merkel endings and lanceolate endings that emanate from large-caliber afferents in the whisker follicles were reduced and showed signs of degeneration. Furthermore, a reduction of piloneural complexes at the intervibrissal hairs were evident, but only in aged rats that showed more severe behavioral sensorimotor disturbances. In contrast, Ruffini endings as well as mechanoreceptors emanating from medium-caliber axons, i.e., transverse lanceolate and reticular endings, appeared normal. (2) A reduction was evident among two sets of unmyelinated epidermal endings; however, the epidermal innervation affiliated with the intervibrissal hairs appeared normal in the aged rat. (3) A loss of sympathetic neuropeptide tyrosine (NPY) or tyrosine hydroxylase-immunoreactive (IR) and somatosensory Calcitonin gene-related peptide (CGRP)-IR perivascular axons was paralleled by an increase in presumed parasympathetic NPY/CGRP-IR axons. (4) Two “novel” networks of fine-caliber axons were observed in the outer and inner root sheaths of the whisker follicles in the aged rat. (5) NPY was present in a population of small-caliber, somatosensory CGRP-IR axons in the aged rat. This may represent a de novo synthesis, since, normally, NPY-like immunoreactivity is not observed in this set of axons. Our results suggest that the sensory impairments occurring with advancing age are part of a peripheral process instigated by changes in nerve-target interactions and/or incapacitation of the neuronal machinery to sustain the axonal integrity.
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  • 380
    ISSN: 1432-1106
    Schlagwort(e): Key words “Central pain” ; Picrotoxin ; Epilepsy ; Acetylcholine ; Cortex ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In this study, we examined the modulation by acetylcholine of electrocorticographical (ECoG) ictal events and spontaneous pain-like behaviors following cortical application of the GABAA antagonist picrotoxin in the awake rat. Distilled water as vehicle, the cholinomimetic substance eserine, and the general muscarinic antagonist atropine were microinjected 10 min before the second microinjection of 2 μg picrotoxin into the hind paw region of the somatomotor cortex (SmI). Under these conditions, we observed that eserine (physostigmine, 1 μg, 10 μg, and 20 μg) did not consistently modify the number of the picrotoxin-induced ECoG spikes and bursts, but instead produced a massive enhancement of the number of hind paw licks compared with vehicle at 10 μg and, to a lesser extent, the number of the stereotyped “turn-in” and “neglected” paws following picrotoxin. In contrast, atropine (l μg, 10 μg, and 20 μg) increased the number of the picrotoxin-induced spikes and bursts at 10 μg and, at all doses, decreased the number of the picrotoxin-induced pain-like symptoms. Statistically significant changes for the number of paw lifts, licks, and “turn-in” paws were observed only with 10 μg. These results tend to show that epilepsy and pain are not strictly related to each other and also emphasize the cortex as a target for interactions between GABA and acetylcholine relative to “central” pain.
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  • 381
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 117 (1997), S. 80-86 
    ISSN: 1432-1106
    Schlagwort(e): Key words Hippocampus ; Commissural fibers ; Reactive sprouting ; Synaptogenesis ; Synaptophysin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Expression of the synaptic vesicle protein synaptophysin was studied in lesion-induced sprouting neurons of the contralateral entorhinal cortex and in the contralateral dentate gyrus using immunocytochemistry at the light- and electron-microscopic level. Perikaryal immunoreactivity for synaptophysin was found between 8 and 10 days postlesion. Light microscopy revealed that synaptophysin immunostaining was present in almost all neurons of layers II and III of the contralateral medial entorhinal cortex. These neurons give rise to the sprouting, crossed temporodentate pathway. In addition, some hilar neurons of the contralateral dentate gyrus, which are the parent cells of sprouting commissural fibers, were immunostained for synaptophysin. Transient immunostaining for synaptophysin was observed within cell bodies and dendrites. Additionally, the cell bodies were outlined by immunoreactive puncta, identified by electron microscopy as nerve terminals. Our results revealed that sprouting neurons express the major synaptic vesicle protein synaptophysin during reactive synaptogenesis in a pattern that reflects biosynthesis and sorting of this protein as seen in developing neurons during synapse formation.
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  • 382
    ISSN: 1432-1106
    Schlagwort(e): Key words Locomotor recovery ; Neural transplantation ; Fictive locomotion ; Serotonin ; 6-Hydroxydopamine ; Zimelidine ; Rat ; Spinal
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Locomotor movements are programmed in a specialised neuronal network that is localised in the central nervous system and referred to as the central pattern generator (CPG) for locomotion. This CPG can be activated by pharmacological agents such as monoamines. The aim of the present study was to try to activate the CPGs by using cells that are supposed to release serotonin locally. Adult chronic spinal rats were injected with embryonic brainstem neurons within the spinal cord under a thoracic transection. This procedure resulted in a monoaminergic reinnervation of the lumbar enlargement. With the help of a specific neurotoxin for noradrenergic neurons (6-hydroxydopamine), it was possible to isolate the serotonergic system. After such transplantation of monoaminergic neurons and even with serotonergic neurons alone, a bilateral, alternating, rhythmic locomotor-like activity recovered in hindlimbs. Furthermore, this locomotor-like activity was clearly facilitated when the re-uptake of serotonin was blocked by zimelidine. Therefore, we conclude that transplanted embryonic serotonergic neurons are able to activate the CPG for locomotion.
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  • 383
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 113 (1997), S. 520-533 
    ISSN: 1432-1106
    Schlagwort(e): Key words Spinal Ia terminations ; Action potentials ; Baclofen ; Calcium influx ; Cat ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, microelectrophoretically administered (–)-baclofen, but not (+)-baclofen, reversibly reduced the duration of the orthodromic action potential of muscle group Ia afferent terminations, but not those of muscle group I afferent myelinated fibres. The presumably submicromolar concentrations are already known to reversibly reduce excitatory transmitter release from muscle group Ia afferent terminations. Action potential durations were estimated from threshold recovery curves after an orthodromic impulse using an extracellular microstimulation technique. Both of these presynaptic effects of (–)-baclofen were blocked by baclofen antagonists, and neither appeared to be reduced by the potassium channel blocking agents tetraethylammonium and 4-aminopyridine. Tetraethylammonium and 4-aminopyridine also did not significantly modify the reduction by (–)-baclofen of monosynaptic field potentials in the lumbar cord of rats anaesthetised with pentobarbitone sodium. In the cat the maximum reduction by (–)-baclofen of termination action potentials was considerably less than that produced by cadmium ions, which, unlike (–)-baclofen, also reduced the action potential duration of group I myelinated fibres. These findings are consistent with a reduction by (–)-baclofen of the influx of calcium through voltage-activated channels in the membrane of group Ia terminations, a proposal which also accounts for the reduction by (–)-baclofen of the release of GABA at axo-axonic depolarizing synapses on these terminations. The results are discussed in relation to the mode of action of (–)-baclofen and the different sensitivities of transmitter release at various central synapses.
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  • 384
    ISSN: 1432-1106
    Schlagwort(e): Key words Forebrain ischemia ; Hyperglycemia ; Hippocampus ; Bioenergetic state ; Cyclosporin A ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  A recent study from this laboratory has shown that brief transient ischemia (2 min 30 s) in normo- and hyperglycemic rats leads to moderate neuronal necrosis in CA1 cells of the hippocampus, of equal density in the two groups. However, hyperglycemic animals failed to depolarize during the ischemia, nor did they show a decrease in extracellular calcium concentration. The present study was undertaken to study the metabolic correlates to these unexpected findings. Normoglycemic (plasma glucose ∼6 mM) and hyperglycemic (∼20 mM) rats were subjected to ischemic periods of 1 min and 2 min 15 s (2 min 30 s with freezing delay considered), and their brains were frozen in situ. Samples of dorsal hippocampus were dissected at –22°C and extracted for the measurement of phosphocreatine (PCr), creatine, ATP, ADP, AMP, glucose, glycogen, and lactate. Normoglycemic animals showed rapid depletion of PCr, ATP, glucose, and glycogen, and a rise in lactate content to 10–12 mM·kg–1 during the ischemia. Hyperglycemic animals displayed a more moderate rate of fall of PCr and ATP, with ATP values exceeding 50% of control after 2 min 30 s. Glycogen stores were largely maintained, but degradation of glucose somewhat enhanced the lactic acidosis. The results demonstrate that hyperglycemic rats maintained ATP at levels sufficient to prevent cell depolarization and calcium influx during the ischemic period. However, the metabolic perturbation observed must have been responsible for the delayed neuronal damage. We speculate that lowered ATP, increased inorganic P, and oxidative stress triggered a delayed mitochondrial permeability transition (MPT), which led to delayed neuronal necrosis. This assumption was supported by a second series of experiments in which CA1 damage in hyperglycemic rats was prevented by cyclosporin A, a virtually specific inhibitor of the MPT.
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  • 385
    ISSN: 1432-1106
    Schlagwort(e): Key words Enkephalin ; GABA ; Basal ganglia ; 6-Hydroxydopamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In Parkinson’s disease the dopaminergic nigrostriatal pathway degenerates, resulting in an imbalance in activity of two pathways of information flow through the basal ganglia. In animal models of the disease, the striatonigral pathway becomes underactive and the striatopallidal pathway becomes overactive. In the present study immunocytochemistry for enkephalin and GABA and anterograde labelling were used to investigate whether morphological plasticity occurs in striatopallidal terminals following unilateral removal of the nigrostriatal dopaminergic pathway. Pallidal terminals were immunostained to reveal enkephalin and examined in the electron microscope (n=399). Immunoreactive synaptic bouton profiles were on average 64% larger on the experimental side 26 days after the lesion. Analysis of their shape revealed that those on the dopamine-depleted side of the brain were more irregular in profile and that their synaptic specialisations were more complex in shape but not significantly different in length. Striatopallidal terminals were also identified by GABA immunocytochemistry combined with anterograde labelling (n=20). Double-labelled boutons were significantly larger in cross-sectional area on the experimental side (57%). Analysis of terminals that were simply labelled by the immunogold method to reveal GABA (n=278) showed no significant differences in size between terminals from the dopamine-depleted and control side. This suggests that a substantial number of GABAergic terminals in the globus pallidus do not belong to the striatopallidal population of terminals. These morphological changes correlate with previous studies suggesting striatopallidal boutons are more active after destruction of dopaminergic input to the neostriatum.
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  • 386
    ISSN: 1432-1211
    Schlagwort(e): Key words CD4 ; Rat ; LEC ; thid ; Chromosomal mapping
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
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  • 387
    ISSN: 1432-1912
    Schlagwort(e): Key words Neocortex ; Cholecystokinin ; Dynorphin ; Amino acids ; Microdialysis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of sulphated cholecystokinin-8 (CCK-8S) on extracellular dynorphin B, aspartate, glutamate and GABA levels in the rat fronto-parietal cortex was investigated with in vivo microdialysis. The peptide was infused through the microdialysis probe trying to mimic local CCK-8S release. Basal levels of dynorphin B were around 20pM, aspartate 100nM, glutamate 600nM and GABA 30nM. CCK-8S (10μM) induced a ≈3-fold increase in extracellular dynorphin B, aspartate and glutamate levels, while GABA levels were only slightly increased. The effect of CCK-8S was restricted to the stimulated neocortex. Systemic pretreatment with the CCKB antagonist, L-365, 260, but not with the CCKA antagonist, L-364, 718, significantly antagonised the effect of CCK-8S on cortical dynorphin B and aspartate release. However, both CCKA and CCKB antagonists inhibited the increase in cortical glutamate levels. Thus, the present results indicate that cortical CCK release exerts a stimulatory modulation on cortical dynorphin B and aspartate release via the CCKB receptor subtype, and on glutamate release via both CCKA and CCKB receptor subtypes. Considering electrophysiological evidence that CCK increases neuronal firing rates in many brain regions, it may be suggested that CCK represents a stimulatory system modulating the function of the neocortex.
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  • 388
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 355 (1997), S. 595-600 
    ISSN: 1432-1912
    Schlagwort(e): Key words Morphine ; Nitric oxide ; Apomorphine ; Oxytocin ; Penile erection ; Yawning ; Paraventricular nucleus of the hypothalamus ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The possible involvement of nitric oxide in the prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning was investigated by measuring the concentration of NO2- and NO3- in the dialysate obtained with a vertical microdialysis probe implanted in the paraventricular nucleus of the hypothalamus of male rats. Either apomorphine (80 µg/kgs.c.) or oxytocin (30 ng i.c.v.) increased significantly basal NO2- and NO3- concentration in the paraventricular dialysate, penile erection and yawning. Morphine (1, 5 and 10mg/kg i.p.) prevented dose-dependently either apomorphine or oxytocin responses when given 15min before apomorphine or oxytocin. Prevention by morphine of apomorphine and oxytocin responses was abolished by naloxone (3mg/kg i.p.) given 15min before morphine. Morphine prevented apomorphine and oxytocin responses also when given in the lateral ventricles or directly in the paraventricular nucleus. In contrast, the selective agonist of the kappa opioid receptor subtype U-69,593 was found to be ineffective. The present results confirm previous findings showing that morphine acts through µ receptors in the paraventricular nucleus to prevent apomorphine and oxytocin-induced penile erection and yawning and suggest that this morphine effect is mediated by a decreased activity of nitric oxide in the paraventricular nucleus of the hypothalamus.
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  • 389
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 355 (1997), S. 689-698 
    ISSN: 1432-1912
    Schlagwort(e): Key words β-adrenoceptors ; β adrenoceptor antagonists ; Celiprolol ; Rat ; Blood pressure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Celiprolol is a β-adrenoceptor antagonist which has desirable ancillary properties since it is relatively cardioselective and can exert direct vasodilator and bronchodilator effects. Here agonist and antagonist effects of celiprolol at cardiac β1- and vascular β2-adrenoceptors were determined under in vivo conditions in the rat. All experiments were carried out in catecholamine-depleted, pentobarbital anesthetized and vagotomized rats, placed under artificial respiration. I.v. administrations were madevia the femoral vein. Blood pressure was measured from the cannulated right carotid artery and heart rate was recorded with a cardiotachometer. Celiprolol (10 µg/kg to 1 mg/kg i.v.) produced dose-related increases in heart rate and decreases in mean carotid artery blood pressure which were of longer duration than those mediated by standard agonists of β1-(isoprenaline) or β2-(salbutamol) adrenoceptors respectively. Although the maximal increase in heart rate by celiprolol (110±4 beats/min, n=7) was approximately half that of isoprenaline (198±1 beats/min, n=5), isoprenaline acted at doses 200-fold lower than celiprolol. Betaxolol (0.03-0.3 mg/kg i.v.), a β1-adrenoceptor antagonist, inhibited strongly and with similar potency the tachycardic effects of celiprolol (DR10 = 45 µg/kg i.v.) as well as isoprenaline (DR10 = 45 µg/kg i.v.). On the other hand, the hypotensive effects of celiprolol and salbutamol were antagonized markedly and with similar potency by ICI118,551, a relatively selective β2-adrenoceptor antagonist (DR10 = 15 and 25 µg/kg i.v. respectively). In rats pretreated with celiprolol (0.03 to 0.3 mg/kg i.v.), the heart rate dose-response curves to isoprenaline were shifted to the right of those determined in matched groups of vehicle-pretreated animals. In this respect, celiprolol was half as potent as betaxolol in blocking cardiac β1-adrenoceptors. Furthermore, celiprolol also antagonized the hypotensive effects of salbutamol, but, in this respect, celiprolol was 90-fold less potent than ICI 118,551. In conclusion, these results clearly indicate that celiprolol has the ability of stimulating and blocking not only cardiac β1- but also vascular β2-adrenoceptors. The effects on cardiac β1-adrenoceptors as well as the agonism of β2-adrenoceptors are produced by similar doses of celiprolol. These doses are notably lower than those necessary to block β2-adrenoceptors. Thus, this pharmacological profile, which has also been demonstrated in humans, indicates that celiprolol is a modulator of cardiac β1-adrenoceptors with vascular β2-adrenoceptor agonist properties.
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  • 390
    ISSN: 1432-1912
    Schlagwort(e): Key words γ2-MSH (γ2-melanocyte-stimulating ; hormone) ; Blood pressure ; Heart rate ; Prazosin ; Metoprolol ; SR 49059 ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract γ2-Melanocyte-stimulating hormone (γ2-MSH) and related melanotropins have been shown to have various cardiovascular effects, including acute, short-lasting increases in blood pressure (MAP) and heart rate (HR). γ2-MSH, administered intravenously, dose-dependently increased MAP and HR with an ED50 of approximately 30 nmol/kg and a maximal effect on MAP of approximately 55 mm Hg and on HR of around 70 beats per minute. Intravenous (i.v.) pretreatment with the α1-adrenoceptor antagonist, prazosin, caused the dose-response curve for the effect of γ2-MSH on MAP to shift to the right with a decrease in slope, whereas it had no effect on the dose-response curve for the effect on HR. I.v. pretreatment with the β1-adrenoceptor antagonist, metoprolol, had no effect on the dose-response curve for the effect of γ2-MSH on MAP, but it caused the dose-response curve for the effect of the peptide on HR to shift to the right with a decrease in slope. Neither i.v. nor intracerebroventricular (i.c.v.) administration of the vasopressin V1A receptor antagonist, SR 49059 ((2S) 1-[(2R 3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide), had significant effects on the dose-response curves for the effects of the peptide on either MAP or HR. The doses of prazosin, metoprolol and SR 49059 were found to be effective in counteracting the effects of agonists for these receptors (phenylephrine, isoprenaline and [Arg8]vasopressin, respectively). Taken together, these results support the postulate that the effects of γ2-MSH are, at least partially, due to an increase in sympathetic outflow to the periphery (Gruber and Callahan (1989), Am J Physiol 257: R681-R694), and that this increase leads to increased activation of vascular α1-adrenoceptors and cardiac β1-adrenoceptors. If, as was suggested by these authors, γ2-MSH acts via activation of a central vasopressin system, it is via a vasopressin receptor subtype other than the vasopressin V1A receptor, since i.c.v. administration of a selective vasopressin V1A receptor antagonist failed to interfere with the pressor and cardioaccelerator effects of γ2-MSH.
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  • 391
    ISSN: 1432-1912
    Schlagwort(e): Key words N-Methyl-D-aspartate (NMDA) antagonists ; Locomotion ; Stereotypy ; Catalepsy ; Basal ganglia ; Dopamine antagonists ; Dopamine metabolism ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of systemic administration of the non-competitive N-methyl-D-aspartate (NMDA) antagonists dextrorphan (10–40mg/kg, i.p.) and [±]-5-aminocarbonyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine (ADCI) (25–70mg/kg, i.p.) on basal ganglia-mediated behaviour and on forebrain dopamine metabolism were investigated in rats. Dextrorphan increased locomotor activity but did not induce stereotyped sniffing. ADCI failed to produce any significant motor stimulant and motor depressant actions. Both dextrorphan and ADCI dose-dependently antagonized catalepsy induced by the D-1 dopamine receptor antagonist SCH 23390 or the D-2 dopamine receptor antagonist haloperidol. Only the highest doses of dextrorphan and ADCI increased dopamine metabolism in the prefrontal cortex and/or in the nucleus accumbens, but not in the dorsal striatum. Our results show that dextrorphan and ADCI produce some of the behavioural effects (antagonism of experimentally induced catalepsy) and neurochemical actions (regionally selective stimulation of dopamine metabolism) that have previously been observed in the prototypical non-competitive NMDA antagonist, dizocilpine. The failure of ADCI to induce hyperlocomotion and stereotypy suggests that anticataleptic doses of ADCI may be devoid of the psychotomimetic actions commonly associated with non-competitive blockade of NMDA receptor function.
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  • 392
    ISSN: 1432-1912
    Schlagwort(e): Key words Daily rhythms ; Heart rate ; Temperature ; Locomotor activity ; Anaesthesia ; Ether ; Ketamine ; Rat ; Telemetry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The aim of this study was to evaluate the effect of anaesthesia (ether or ketamine) on daily rhythms of temperature (T), heart rate (H) and locomotor activity (A) in unrestrained rats by using implanted radio-telemetry transmitters. T, H and A were measured every 10min, in Wistar male rats, and analysed using Cosinor. The mean±SEM days needed, after surgical implantation, to detect a daily rhythm in H, T and A were also assessed. Six rats were anaesthetized for about 50min either by ketamine or ether in a 3 by 3 cross-over design. Mesors, amplitudes and acrophases of T, H and A were calculated three days before (D-3; D-2; D-1), the day of anaesthesia (D0) as well as the three following days (D1; D2; D3). ANOVA was performed in order to detect, firstly a possible effect due to the order of application of anaesthesia, secondly a significant difference between ether or ketamine-induced anaesthesia and finally a modification of the mesors, amplitudes and acrophases of T, H and A, induced by each anaesthesia, for D0, D1, D2 and D3 when compared to D-1. Our results indicate: (1) Alterations of the acrophases, mesors and amplitudes, except for the amplitude of A, of the daily rhythms of T, H and A on D0 of ketamine anaesthesia while regarding ether anaesthesia only amplitude of T and H and acrophase of A were modified on D0. Some of these modifications were still observed on the days following anaesthesia. A significant difference between ether and ketamine-induced anaesthesia was also observed. (2) A non-detection of T, H and A daily rhythms after surgical implantation, which was not observed after injection of either ether or ketamine alone. Almost 10 days were needed to detect a significant daily rhythm for T, H and A. The authors suggest that, the general anaesthetic agent was responsible for a perturbation of the mesors, amplitudes and acrophases of the daily rhythms of H, T and A while the non-detection of these rhythms after implantation was more due to the surgical aggression.
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  • 393
    ISSN: 1432-1912
    Schlagwort(e): Key words Blood pressure ; GR127935 ; Hypotension ; 5Hydroxytryptamine ; 5ht7Receptor ; Rat ; Sumatriptan
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract It has been suggested that the late hypotensive response to serotonin (5hydroxytryptamine; 5HT) in vagosympathectomized rats is mediated by ‘5HT1like’ receptors since this effect is mimicked by 5carboxamidotryptamine (5CT), is not modified by cyproheptadine, ketanserin or MDL72222, but it is blocked by methysergide. The present study was set out to reanalyze this suggestion in terms of the classification schemes proposed in 1994 and 1996 by the NCIUPHAR subcommittee on the classification and nomenclature of 5HT receptors. I.v. bolus injections of 5CT (0.010.3μg·kg1), 5HT (130μg·kg1) and 5methoxytryptamine (5MeOT; 130μg·kg1) produced dosedependent hypotensive responses with a rank order of agonist potency: 5CT 〉〉 5HT ≥ 5methoxytryptamine with sumatriptan (301000μg·kg1) inactive. The depressor responses to 5HT and 5CT were not attenuated by i.v. GR127935 (3003000μg·kg1) or equivalent volumes of saline. In contrast, lisuride, methiothepin, mesulergine, metergoline and clozapine dose-dependently antagonized the responses to 5HT and 5CT; the rank order of apparent pA2 values against 5HT and 5CT, respectively, was: lisuride (7.7; 7.8) 〉 methiothepin (6.8; 7.0) ≥ mesulergine (6.4; 6.6) 〉 clozapine (5.7; 5.8); metergoline displayed variable potencies (5.6; 6.4). Except for lisuride, which also affected isoprenalineinduced hypotension, the antagonism by the other drugs was selective. Based upon the above rank order of agonist potency, the blockade by a series of drugs showing high affinity for the cloned 5ht7 receptor and the lack of blockade by GR127935, our results indicate that the 5HT receptor mediating hypotension in vagosympathectomized rats is operationally similar to other putative 5ht7 receptors mediating vascular and nonvascular responses (e.g. relaxation of the rabbit femoral vein, canine coronary and external carotid arteries and guineapig ileum as well as feline tachycardia).
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  • 394
    ISSN: 1432-1912
    Schlagwort(e): Key words Urinary bladder ; Hyperreflexia ; Tachykinin antagonists NK1 receptors ; Tachykinin antagonists ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study investigates the role of tachykinin NK1 and NK2 receptors in motor responses induced by the intravesical instillation of capsaicin in urethane-anaesthetized rats. SR 140,333 (1 µmol/kg, i.v.), a non-peptide NK1 receptor antagonist, abolished urinary bladder contractions induced by the selective NK1 receptor agonist [Sar9]SP-sulfone (0.1-100 nmol/kg, i.v.) without affecting those induced by the NK2 receptor agonist [ßAla8]NKA(4-10). MEN 11,420 (100 nmol/kg, i.v.), a cyclic peptide NK2 receptor antagonist, abolished bladder contractions induced by [ßAla8]NKA(4-10) (0.3-300 nmol/kg, i.v.) without modifying those induced by [Sar9]SP-sulfone. Intravesical instillation of capsaicin (6 nmol/0.6 ml/rat) produced a motor response consisting in a primary contraction followed by a series of high amplitude phasic contractions. The intravesical instillation of saline (0.6 ml/rat) produced a primary contraction of lower amplitude with respect to that induced by capsaicin and the total area under the curve was also lower in saline-instilled rats, however the number and the amplitude of phasic contractions was similar to that induced by capsaicin. MEN 11,420 (100 nmol/kg, i.v.) did not modify motor responses induced by the intravesical administration of saline. In contrast, in capsaicin-instilled rats, MEN 11,420 (100 nmol/kg, i.v.) reduced the primary contraction, the area under the curve and also the number of phasic contractions. SR 140,333 (1 µmol/kg, i.v.) reduced the primary contraction but not other parameters. The combination of SR 140,333 (1 µmol/kg, i.v.) and MEN 11,420 (100 nmol/kg, i.v.) produced an additive inhibitory effect on the primary contraction but not a further inhibition on other parameters with respect to that observed with MEN 11,420 alone. In hexamethonium (110 µmol/kg, i.v.)-pretreated animals the intravesical instillation of capsaicin produced a tonic contraction having greater amplitude and area than that induced by saline. MEN 11,420, but not SR 140,333, significantly reduced the bladder response to capsaicin in hexamethonium-pretreated rats. Again, the combined administration of MEN 11,420 and SR 140,333 did not produce further inhibitory effect in comparison to MEN 11,420 alone. It is concluded that the motor responses induced by the intravesical instillation of capsaicin are mediated by the activation of peripheral tachykinin NK2 receptors.
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  • 395
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 611-618 
    ISSN: 1432-1912
    Schlagwort(e): Key words Hippocampus ; EPSP ; IPSP ; GABA ; NMDA ; Epilepsy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Previous behavioural and electrophysiological studies have indicated that levetiracetam (ucb LO59) acts as an anticonvulsant drug in vivo. The purpose of the present study was to investigate the effects of levetiracetam on normal synaptic transmission and epileptiform activity in vitro. Intracellular recordings were obtained from the CA3 subfield of the rat hippocampal slice preparation. Levetiracetam in a concentration of 10 μM did not influence basic cell properties or normal synaptic transmission evoked by subthreshold and suprathreshold stimuli to the commissural pathway. However, it strongly inhibited the development of epileptiform bursting by the γ-aminobutyric acid (GABA)A-receptor antagonist bicuculline (1– 30 μM). Levetiracetam also decreased the size of bursts previously established by bicuculline. In experiments in which the glutamate-receptor agonist N-Methyl-D-Aspartate (NMDA) was used to generate spontaneous bursting, levetiracetam had no effect on the size of the bursts but decreased bursting frequency. The difference in effects of levetiracetam on bicuculline- and NMDA-induced bursting appeared to be dependent on the convulsant used, since in the presence of 10 μM bicuculline, levetiracetam decreased the size of NMDA-bursts to the same extent as the size of synaptically evoked bicuculline-bursts but had little effect on bursting frequency. The results show that under our experimental conditions, levetiracetam did not alter the components of normal synaptic transmission. However, levetiracetam at the concentrations studied inhibited epileptiform bursting induced by bicuculline and NMDA in vitro in a manner consistent with the profile of an antiepileptogenic drug.
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  • 396
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 297-302 
    ISSN: 1432-1912
    Schlagwort(e): Key words Lipid peroxidation ; Free radicals ; Oxidative stress ; In vitro ; In vivo ; Antioxidant ; Antiestrogen ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The aim of the present study was to investigate antioxidativity of the triphenylethylene antiestrogen toremifene. Toremifene and its structural analogues were studied for their ability to inhibit chain reactions of lipid peroxidation and to act as scavengers of free radicals in vitro, and the effects of toremifene were compared to those of the estrogens, tamoxifen and known antioxidants. Moreover, the in vivo antioxidativity of toremifene was tested in a long-term experiment with rats. The ability of toremifene to prevent lipid peroxidation was assayed in two different test systems. In the first assay (initiated with ascorbate/ADP-FeCl3, detection by the formation of TBA-reactive material) toremifene was found to act as an efficient membrane antioxidant with an IC50-value (18 μM) comparable to that of tamoxifen (26 μM) and α-tocopherol (43 μM). Toremifene derivatives 4-hydroxytoremifene (IC50 = 8 μM) and Fc 1159 (IC50 = 31 μM), as well as diethylstilbestrol (IC50 = 17 μM) were also active while estradiol showed only weak antioxidativity (IC50 = 300 μM) in this test system. In the other assay (peroxidation initiated with t-butylhydroperoxide, detection by luminol-enhanced chemiluminescence) toremifene prevented lipid peroxidation only at high concentrations (IC50 = 450 μM) but the metabolite 4-hydroxytoremifene (IC50 = 0.18 μM), estradiol (IC50 = 4.6 μM) and diethylstilbestrol (IC50 = 1.7 μM) showed potent antioxidant activity. The potency of 4-hydroxytoremifene even exeeded that of α-tocopherol (IC50 = 2.0 μM) and butylated hydroxyanisole (IC50 = 1.1 μM). Toremifene was found to have some superoxide anion but no peroxyl radical scavenging activity. Interestingly, diethylstilbestrol turned out to be a potent scavenger of peroxyl radicals. Treatment of female Sprague-Dawley rats with toremifene (12 or 48 mg/kg) was found to decrease serum levels of lipid peroxides. This was seen at various time points (2 days, 5 weeks, 6 and 12 months) during long-term administration of toremifene to rats, and results obtained with two different methods (diene conjugation, TBA-reactive material) gave similar results. The present study thus showed that (i) like steroidal estrogens and tamoxifen toremifene is a potent membrane antioxidant in vitro, (ii) the antioxidant action of toremifene is not due to scavenging of free radicals and, importantly, (iii) toremifene acts antioxidatively also in living organisms in vivo.
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  • 397
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 341-347 
    ISSN: 1432-1912
    Schlagwort(e): Key words Complex partial seizure ; Diphenylhydantoin ; Epileptic focus ; Limbic system ; Rat ; Threshold
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Phenytoin is a major antiepileptic drug for treatment of limbic seizures. The effect of phenytoin on the generation and spread of seizure activity was studied in a rat model of this type of seizures. Sprague-Dawley and Wistar rats were implanted with a stimulation and recording electrode in the basolateral amygdala. Naive Sprague-Dawley rats showed an increase in current intensity necessary for eliciting afterdischarges (afterdischarge threshold) of about 200% after administration of phenytoin (75 mg/kg i.p.), while seizure severity at threshold was increased compared to controls. Afterdischarge and seizure durations were significantly prolonged under phenytoin. This result suggests that phenytoin can exert a potent anticonvulsant effect on the generation of focal seizure activity, but it does not suppress or may even increase on-going afterdischarge activity once it occurs. Following amygdala kindling in Wistar rats, administration of phenytoin again resulted in an increase in the afterdischarge threshold. However, all rats still showed generalized seizures, and epileptic afterdischarges could be recorded in various limbic brain regions at threshold current. This result suggests that phenytoin can increase the threshold for generation of epileptic discharges in kindled rats, but is not able to prevent the development of generalized seizure activity and the spread of afterdischarges within the limbic system when focal activity is initiated. We conclude that phenytoin is able to suppress focal seizure activity in the amygdala kindling model of the rat. However, it does not prevent the spread of seizure activity originating in the limbic system. Therefore, a decrease in focal seizure susceptibility seems to be the primary target for phenytoin’s anticonvulsant action.
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  • 398
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 738-745 
    ISSN: 1432-1912
    Schlagwort(e): Key words [3H]-Acetylcholine release ; Rat ; caudatoputamen ; Cholinergic interneurons ; Glycine ; receptors ; Serine ; Strychnine ; Ethanol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the present study acute effects of ethanol on [3H]-acetylcholine ([3H]-ACh) release induced by activation of strychnine-sensitive glycine receptors in superfused slices of rat caudatoputamen were investigated. The glycine-evoked [3H]-ACh release (lg EC50 = –4.10, CI95 = [–4.14, –4.05]) was inhibited by strychnine in a competitive manner (pA2 = 6.86, CI95 = [6.61, 7.08]). Release of [3H]-ACh could also be induced by L-serine. L-serine was less potent than glycine (lg EC50 = –2.61, CI95 = [–2.69, –2.52]). Both glycine and L-serine showed similar maximum effects (Emax(glycine) = 1.34, CI95 = [1.24, 1.45]; Emax(L-serine) = 1.19, CI95 = [1.09, 1.32]). Ethanol at concentrations of 2‰ (= 34 mM) and 4‰ (= 68 mM) inhibited glycine-evoked [3H]-ACh release in a manner like the competitive antagonist strychnine, however with lower potency. The pA2 of ethanol was 1.19, CI95 = [0.85, 1.41], at 2‰ [v/v] and 1.51, CI95 = [1.19, 1.78] at 4‰ ethanol. Similar to its action on glycine-evoked [3H]-ACh release, ethanol at 4‰ [v/v] also inhibited L-serine-evoked transmitter release in a competitive-like fashion (pA2 = 0.83, CI95 = [–0.15, 1.18]). We conclude, that strychnine-sensitive glycine receptors, mediating [3H]-ACh release in the rat caudatoputamen, might represent a new site of action of ethanol.
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  • 399
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 129 (1997), S. 249-256 
    ISSN: 1432-2072
    Schlagwort(e): Key words Nicotine ; Acute tolerance ; Ibogaine ; Dopamine ; Microdialysis ; In vivo ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract There is increasing evidence that the rewarding effect of nicotine is mediated by the mesolimbic dopamine system. The first objective of this study was to examine the dopamine response to repeated IV infusions of nicotine. Using in vivo microdialysis in awake and freely moving male Sprague-Dawley rats, we demonstrated that IV nicotine infusions (0.16 mg/kg or 0.32 mg/kg per infusion) produced increases in extracellular dopamine levels that were dose- and infusion order-dependent. Acute tolerance was evidenced by the smaller dopamine response produced by a second infusion of nicotine, administered 1 h after the first one. Tolerance was reversible, since the dopamine response to a second infusion of nicotine was unchanged when the interval between the infusions was increased to 3 h. Ibogaine, an alkaloid found in Tabernanthe iboga, is claimed to decrease smoking and to have an anti-nicotinic action. The second objective of this study was to establish whether this claim has any neurochemical basis. Pretreatment with ibogaine (40 mg/kg, IP) 19 h prior to the first nicotine infusion (0.32 mg/kg per infusion) significantly attenuated the increase in extracellular dopamine levels induced by the nicotine infusions, suggesting that ibogaine may decrease the rewarding effect of nicotine.
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  • 400
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 130 (1997), S. 41-58 
    ISSN: 1432-2072
    Schlagwort(e): Key words Cocaine ; Drug discrimination ; Dopamine (DA) ; Human ; Rat ; Reuptake inhibitor ; Reinforcing effects ; Self-administration ; Serotonin (5-HT) ; 5-HT1A ; 5-HT2 ; 5-HT3 ; Subjective effects ; Stimulus effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The purpose of the present manuscript is to review the current status of the role of serotonin (5-hydroxytryptamine; 5-HT) systems in the stimulus and reinforcing properties of cocaine in non-humans and the subjective effects of cocaine in humans. Review of the current literature suggests that general enhancement (via precursor administration) or depletion of brain 5-HT content (via neurotoxin administration or tryptophan depletion) impact the reinforcing effects of cocaine in non-humans and its subjective effects in humans. Selective 5-HT reuptake inhibitors (SSRIs) enhance the discriminability of cocaine and decrease cocaine self-administration in animals, although data to the contrary also exist. Studies in humans suggest that SSRIs attenuate the subjective effects of cocaine in humans. Although few drugs with selectivity for 5-HT2 receptors have been studied systematically, a 5-HT2 agonist and several antagonists show some efficacy in enhancing and reducing, respectively, the reinforcing effects of cocaine in non-humans. Limited data from humans suggest that a 5-HT2 antagonist may also decrease the subjective effects of cocaine; thus, 5-HT2 compounds deserve further attention. The majority of studies evaluating the 5-HT3 antagonists have reported negative results across all paradigms. In summary, while the functional significance of 5-HT receptors has not been fully elucidated, these data suggest that changes in serotonergic activity can modulate the effects of cocaine in both animals and humans under a variety of experimental conditions. One commonality among the studies with positive findings is that cocaine effects are only partially modified by 5-HT agents regardless of the direction of change.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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