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  • Life and Medical Sciences  (48,545)
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  • 101
    ISSN: 1432-198X
    Keywords: Key words Hypercalciuria ; Idiopathic hypercalciuria ; Bone mineral content ; 1 ; 25-Dihydroxyvitamin D ; Furosemide ; Ammonium chloride ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The relationship between bone mineral status and hypercalciuria is controversial. The effect on bone composition of different forms of hypercalciuria was studied in female rats made hypercalciuric by 7-week administration of oral furosemide (F, n=12), intraperitoneal 1,25-dihydroxy vitamin D (VD, n=11), or oral ammonium chloride (AC, n=12). Seven untreated rats served as controls (C). Hypercalciuria (mg/100 g per 24 h, mean ±SEM) of F (4.3±0.2), VD (4.1±0.4), and AC (3.9±0.3) groups was of similar intensity (C rats 1.3±0.1, P〈0.01). Weight and length gains and serum CO2, sodium, potassium, calcium, and phosphate were no different among the four groups. Bone was studied by dual-energy X-ray absorptiometry of left tibiae. AC rats had significantly less bone area (1.505±0.018 cm2) than VD and C (1.602±0.020 and 1.587±0.019 cm2). Bone mineral content was decreased in F (0.357±0.007 g) and AC (0.362±0.006 g) compared with VD (0.407±0.008 g) and C (0.389±0.009 g) groups. Bone mineral density was different between F (0.231±0.002 g/cm2) and VD and C rats (0.254±0.004 and 0.245±0.003 g/cm2), and also between AC (0.240±0.003 cm2) and VD rats. In these rat models, hypercalciuria of renal origin (F) and hypercalciuria caused by acid load (AC) adversely impaired bone mass.
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  • 102
    ISSN: 1432-198X
    Keywords: Key words Cystinosis ; Cysteamine ; Renal function ; Rat ; Prenatal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The safety of cysteamine after renal transplantation and during pregnancy is an important issue, since girls with cystinosis are in better health on cysteamine therapy and thus more likely to become pregnant. In the first study, cysteamine was given to pregnant rats on days 6.5–18.5 post conception in oral doses of 0, 37.5, 75, 100, and 150 mg/kg per day. The dams were sacrificed on day 20.5, the fetal kidneys removed and prepared for histological examination. In the second study, cysteamine was given to dams on days 6.5–19.5 post conception in oral doses of 0, 37.5, 50, and 75 mg/kg per day. Dams were allowed to give birth naturally and pups were given cysteamine on days 4–21 to yield the same oral doses of cysteamine given to the dam. Renal function was evaluated on day 35. Histological examination of fetal kidneys revealed no changes even in kidneys from fetuses with growth retardation and malformations. Furthermore, there were no alterations in renal function in offspring on day 35. These findings demonstrate that cysteamine therapy does not affect renal development in the rat. Further investigations will be required to prove whether cysteamine therapy has the potential to affect renal development in the human.
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  • 103
    ISSN: 1432-2072
    Keywords: Key words Ethanol ; Limited access ; Nicotine ; Mecamylamine HCl ; Rat ; Voluntary intake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Observations in humans suggest that the initial use of tobacco occurs in close temporal proximity to experimentation with alcohol. There have been relatively few research reports, however, examining possible interactions between these two agents. The present experiments examined the effect of nicotine exposure on the acquisition of ethanol drinking behavior in a limited access procedure. In experiment 1, rats were presented with 1-h access to ethanol solutions of increasing concentration for a period of 20 days. Subcutaneous injections of nicotine (0.6 or 1.2 mg/kg salt) or vehicle were administered 30 min prior to each ethanol presentation. Experiment 2 used a similar method, but rats were presented with water along with ethanol during the 1-h test session. Mecamylamine, a nicotinic receptor antagonist, was administered 30 min prior to the nicotine treatment. Nicotine was seen to produce a dose-dependent increase in ethanol drinking behavior which commenced at the 5% ethanol concentration and continued at 8% and again at 10%. In the second experiment, mecamylamine was observed to block completely the nicotine-induced increase in ethanol drinking behavior. The findings suggest that exposure to nicotine can facilitate the acquisition of ethanol drinking behavior in naive rats and that this effect is mediated by nicotine’s interaction at the nicotinic-cholinergic receptor.
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  • 104
    ISSN: 1432-2072
    Keywords: Key words Chlordiazepoxide ; FG 7142 ; Rat ; Diencephalic amnesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The intralaminar thalamic nuclei (ILn) have been implicated as a critical site of pathology in amnesia. Lesions of the ILn have been found to produce behavioral effects comparable to benzodiazepine (BDZ) receptor agonists. We compared the effects of chlordiazepoxide (CDP), a BDZ agonist, and FG 7142, a partial inverse agonist at the BDZ receptor, in rats with thalamic lesions and in unlesioned controls. Delayed matching-to sample (DMS) performances were studied during treatment with ascending doses of CDP, counterbalanced trials with 2.5 mg/kg CDP and saline, ascending doses of FG 7142, and (for unlesioned controls only) counterbalanced trials with saline and higher doses of CDP. CDP had effects similar to the ILn lesion, decreasing response speed and percent correct responding in a delay-independent fashion. These effects were additive with the impairments associated with the ILn lesion. The effects of FG 7142 were more complex. At lower doses, it increased response speed without affecting response accuracy. At higher doses, it diminished both the speed and the accuracy of DMS responding. These results support the hypothesis that ILn lesions and BDZ agonists have similar effects on DMS performance. The biphasic effects observed for FG 7142 are consistent with other evidence that low doses of this drug enhance while higher doses impair memory performance. Although DMS accuracy was not improved, the enhancement observed for response speed provides evidence that partial inverse BDZ agonists have potential utility as treatments for cognitive impairments associated with amnesia.
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  • 105
    ISSN: 1432-2072
    Keywords: Key words Male sexual behavior ; Sexual impotence ; Plant extracts ; Turnera diffusa ; Pfaffia paniculata ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sexually potent and sexually sluggish/impotent male rats were treated orally with different amounts of Turnera diffusa and Pfaffia paniculata fluid extracts (0.25, 0.50, 1.0 ml/kg). While having no effect on the copulatory behavior of sexually potent rats, both plant extracts – singly or in combination – improved the copulatory performance of sexually sluggish/impotent rats. The highest dose of either extract (1 ml/kg) (as well as the combination of 0.5 ml/kg of each extract) increased the percentage of rats achieving ejaculation and significantly reduced mount, intromission and ejaculation latencies, post-ejaculatory interval and intercopulatory interval. Neither extract affected locomotor activity. These results seem to support the folk reputation of Turnera diffusa and Pfaffia paniculata as sexual stimulants.
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  • 106
    ISSN: 1432-2072
    Keywords: Key words BC264 ; Cholecystokinin ; CCKB receptor ; Memory ; Ageing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: The implication of CCKB receptors in cognitive processes is far from fully understood. Objective: The present study investigated the effect of propionyl-BC264, a selective agonist of CCKB receptors, in young and old rats. Methods: Cognitive functions were studied in a two-trial recognition memory task developed in our laboratory. Results: It was shown that propionyl-BC264 enhanced information processing in young as well as in old rats when injected (10 μg/kg; IP) immediately after the acquisition phase and before the retrieval trial but not before the acquisition trial. This cognitive enhancing effect was blocked by prior administration of L 365,260, a selective CCKB receptor antagonist. Conclusions: In view of the fact that BC264 is devoid of anxiogenic effects, it could be of value in the treatment of cognitive impairments associated with both normal and pathological ageing.
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  • 107
    ISSN: 1432-2072
    Keywords: Key words Baclofen ; Cocaine ; Extinction ; Intravenous self-administration ; Maintenance dose ; Rat ; Reinstatement of responding ; Relapse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Recent studies suggest that the GABAB receptor agonist, baclofen, may be a useful pharmacotherapy for cocaine abuse. Objectives: To investigate further the effects of baclofen on maintenance and reinstatement of cocaine-reinforced behavior in rats. Methods: Two groups of rats were trained to self-administer IV cocaine (0.2 or 0.4 mg/kg per infusion) during daily 7-h sessions under a fixed-ratio 1 schedule. Rats were pretreated with baclofen (1.25, 2.5 or 5 mg/kg IP) or saline before the session for 5 consecutive days. An additional group of rats was trained to self-administer IV cocaine (0.4 mg/kg per infusion) during the first 2 h of daily 7-h sessions. Cocaine was replaced by saline for the remaining 5 h of the session. Once behavior had stabilized over the 7-h period, priming injections of saline (IV), cocaine (3.2 mg/kg IV) or baclofen (1.25 or 2.5 mg/kg IP) were administered prior to hour 4. Injections of baclofen (1.25 or 2.5 mg/kg IP) or saline were also given before priming injections of cocaine. Results: Pretreatment with the two higher doses of baclofen (2.5 and 5 mg/kg) decreased the number of cocaine infusions in both maintenance groups (0.2 and 0.4 mg/kg) over the 5-day treatment period. Baclofen had a greater suppressant effect on responding maintained by the lower dose of cocaine. Priming injections of baclofen (1.25 and 2.5 mg/kg) or saline did not reinstate responding. However, these same doses of baclofen dose-dependently reduced the reinstatement of responding produced by priming injections of cocaine. Conclusions: 1) The magnitude of the suppressant effects of baclofen on maintenance of cocaine self-administration depends upon the maintenance dose, 2) baclofen may be useful in preventing reinstatement of cocaine-seeking behavior, and 3) compared to maintenance, reinstatement of responding is more sensitive to the suppressant effects of baclofen.
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  • 108
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 143 (1999), S. 318-321 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Cotinine ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: The route of nicotine administration between animal models and humans is very different and further investigation by determining levels of nicotine entering into the circulatory system is warranted. Objective: The present study addresses the validity of the rat self-administration procedure by comparing plasma levels of nicotine in the rat with levels reported in smokers following cigarette consumption. Methods: Plasma levels of nicotine and its metabolite cotinine were measured in 17 rats following intravenous self-administration of a range of nicotine doses (0.015, 0.03 and 0.06 mg/kg per infusion). Results: The two larger unit doses supported reliable self-administration behaviour with no overall difference in the patterns of nicotine intake. However, the total nicotine intake over the 2-h session was related to unit dose and this correlated highly with nicotine and cotinine levels measured in blood collected from the tail vein. On average, cotinine levels (50–200 ng/ml) were approximately 2-fold higher than nicotine levels (40–120 ng/ml) in plasma. Following an extinction test for one session in which saline was substituted for nicotine, no change in behaviour was observed in the two groups, while plasma levels of nicotine and cotinine dropped to nominal levels. Conclusions: The concentrations of nicotine attained following nicotine self-administration appear to be similar to levels reported in smokers after cigarette consumption, providing further validation of this procedure as an animal model of nicotine dependence.
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  • 109
    ISSN: 1432-2072
    Keywords: Key words NMDA (N-methyl-D-aspartate) ; Schizophrenia ; Prepulse inhibition (PPI) ; Sensory gating ; P50 ; Auditory evoked potentials (AEP) ; Ketamine ; d-Amphetamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Schizophrenic patients suffer from deficits in information processing. Patients show both a decrease in P50 gating [assessed in the conditioning-testing (C-T) paradigm] and prepulse inhibition (PPI), two paradigms that assess gating. These two paradigms might have a related underlying neural substrate. Gating, as measured in both the C-T paradigm (the gating of a component of the auditory evoked potential (AEP)], and PPI can easily be measured in animals as well as in humans. This offers the opportunity to model these information processing paradigms in animals in order to investigate the effects of neurotransmitter manipulations in the brain. In order to validate the animal model for disturbances in AEP gating, d-amphetamine (0.5 and 1 mg/kg, IP) was administered. Gating of an AEP component was changed due to injection of d-amphetamine (1 mg/kg) in the same way as seen in schizophrenic patients: both the amplitude to the conditioning click and the gating were significantly reduced. Next, the effect of the N-methyl-D-aspartate (NMDA) antagonist ketamine (2.5 and 10 mg/kg, IP) was investigated to assess its effects in the two gating paradigms. It was found that ketamine (10 mg/kg) did not affect gating as measured with components of the AEP. However, ketamine (10 mg/kg) disrupted PPI of the startle response to the extent that prepulse facilitation occurred. Firstly, it is concluded that AEP gating was disrupted by d-amphetamine and not by ketamine. Secondly, PPI and the C-T paradigm reflect distinct inhibitory sensory processes, since both paradigms are differentially influenced by ketamine.
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  • 110
    ISSN: 1432-2072
    Keywords: Key words Dezocine ; Morphine ; 7-OH-DPAT ; Quinpirole ; SKF38393 ; SCH23390 ; Rat ; Warm-water tail-withdrawal ; Antinociception
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: The purpose of the present investigation was to evaluate the effects of the D3 agonist (±)-7-hydroxy-dipropylaminotetralin (7-OH-DPAT), various dopamine (DA) agonists and DA antagonists on the antinociceptive effects of μ opioids. Methods: Antinociception was assessed using a warm-water tail-withdrawal procedure in rats. Results: The μ opioids morphine (0.3–10 mg/kg) and dezocine (0.03–3.0 mg/kg) produced dose-dependent increases in antinociception with maximal effects obtained at the higher doses tested. Pretreatment with the putative D3 agonist 7-OH-DPAT (1.0–10 mg/kg) produced a dose-dependent attenuation of the antinociceptive effects of morphine and dezocine. At the highest dose of 7-OH-DPAT tested, the morphine dose-effect curve was shifted rightward by approximately 1.5 log units and the dezocine curve by greater than 2.3 log units. The (+)-isomer of 7-OH-DPAT (1.0 and 3.0 mg/kg) also shifted the morphine dose-effect curve to the right in a dose-dependent manner. The DA D3/D2 agonist (−)-quinpirole (0.1–10 mg/kg) attenuated the effects of morphine, but these effects were small in magnitude, not dose-dependent and observed only under a limited set of conditions. The DA D2/D3 antagonist spiperone failed to alter the morphine dose-effect curve, but reversed the effects of 7-OH-DPAT on morphine antinociception. Pretreatment with the DA D1 agonist (±)-SKF38393 (1.0 and 10 mg/kg) and the D1 antagonist (+)-SCH23390 (0.1 and 1.0 mg/kg) failed to alter the morphine dose-effect curve. Conclusion: The finding that 7-OH-DPAT markedly attenuated the effects of morphine and that these effects were reversed with spiperone suggests that activity at the D3, and possibly the D2, receptor can modulate μ agonist-induced antinociception.
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  • 111
    Electronic Resource
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    Springer
    Psychopharmacology 144 (1999), S. 311-315 
    ISSN: 1432-2072
    Keywords: Key words Anxiety ; ACTH ; Corticosterone ; GH ; Stress ; Anxiolytic ; Chlordiazepoxide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Social isolation is anxiogenic and may change the effects of anxiolytic drugs. These effects are generally attributed to ”isolation stress”. However, isolation does not affect basal corticosterone levels; thus, it cannot be considered stressful. On the contrary, isolation deprives animals of mild daily stressors that are inherent to social life. Since mild stressors were shown to be anxiolytic in rats, it was postulated that short-term, repeated stressors may abolish the effects of isolation. Objectives: The aim of the present study was to investigate whether short-term, repeated, mild social stress can abolish the consequences of isolation on anxiety and on the effects of chlordiazepoxide. Methods: Rats were housed in groups or in individual cages for 5 days (isolates). Half of isolates were daily submitted to the attacks of a resident rat for 30 min per day, on 4 consecutive days (stressed isolates). On day 5, rats were treated either with vehicle or with chlordiazepoxide and submitted to the elevated plus-maze test. Endocrinological consequences of experimental manipulations were assessed in a different set of rats. Results: Plasma ACTH and corticosterone levels were similar in the three groups. Weight gain was higher, while plasma growth hormone was lower in stressed isolates, both effects being consistent with a mild stress. Isolation had a clear anxiogenic effect. This effect was completely abolished by the daily experience of social stress. Chlordiazepoxide had a significant anxiolytic effect in all three groups. Its effects on classical plus-maze variables did not differentiate the three groups. However, chlordiazepoxide decreased risk assessment activity only in isolates. Conclusions: The lack of appropriate endocrinological changes challenges the concept of ”isolation stress”. However, isolation was anxiogenic in our study and it also induced subtle changes in the effects of chlordiazepoxide. It appears that mild daily stressors have a protective effect against the effects of isolation.
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  • 112
    ISSN: 1432-2072
    Keywords: Key words GABAA receptor ; Propofol ; Midazolam ; NMDA receptor ; Ketamine ; Noradrenaline ; Medial prefrontal cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: N-Methyl-d-aspartate (NMDA) receptor antagonism and GABAA receptor activation are believed to be critical targets for general anesthetic action. However, as NMDA antagonism of intravenous anesthetic agents causes post-anesthetic emergence reactions such as hallucination and agitation, while the GABAA-mimetic intravenous anesthetic agents do not, these two classes of intravenous anesthetic agents produce differential clinical profiles. Objective: We have investigated the differential effects of the GABAA agonists propofol and midazolam and the NMDA antagonist ketamine on noradrenaline release from the medial prefrontal cortex of the rat using microdialysis, as noradrenergic neurons have a role to play in anesthesia and are known to be important in the control of sleep, attention and learning. Methods: Twenty-one male Wistar rats (200– 270 g) were randomly allocated into three groups: ketamine 100 mg.kg–1 (n=6), propofol 60 mg.kg–1 (n=8) and midazolam 5 mg.kg–1 (n=7) IP. A unilateral guide cannula was implanted stereotaxically into the medial prefrontal cortex under pentobarbital anesthesia (50 mg.kg–1 IP). Forty-eight hours later, a dialysis probe was inserted through the guide cannula, and perfused with an artificial cerebrospinal fluid solution containing 1 mM pargyline. Following an equilibration period, samples of dialysate were collected every 10 min. Noradrenaline content was measured by high-performance liquid chromatography using an electrochemical detector. Results: Anesthesia times, defined as the duration between the loss of righting reflex and recovery, were 24.7±5.6 (SEM), 20.5±1.9 and 25.2±1.5 min for propofol, midazolam and ketamine, respectively (no significant between-group differences). Both GABAA agonists, propofol and midazolam, significantly decreased noradrenaline release (75% and 71% of basal release, respectively). The NMDA antagonist ketamine markedly increased noradrenaline release (413% of basal). Conclusion: These data suggest that different clinical profiles observed with these two classes of sedatives may result from changes in noradrenaline release from the medial prefrontal cortex.
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  • 113
    ISSN: 1432-2072
    Keywords: Key words Compulsion ; Addiction ; Cocaine ; Amphetamine ; Cannabis ; Phencyclidine ; Nucleus accumbens ; Amygdala ; Frontal cortex ; Limbic ; Stimulus-reward association ; Conditioned reward ; Sensitization ; Drug-seeking ; Inhibitory control ; Cognition ; Conditioned stimulus ; Incentive motivational ; Dopamine ; Rat ; Monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Drug abuse and dependence define behavioral states involving increased allocation of behavior towards drug seeking and taking at the expense of more appropriate behavioral patterns. As such, addiction can be viewed as increased control of behavior by the desired drug (due to its unconditioned, rewarding properties). It is also clear that drug-associated (conditioned) stimuli acquire heightened abilities to control behaviors. These phenomena have been linked with dopamine function within the ventral striatum and amygdala and have been described specifically in terms of motivational and incentive learning processes. New data are emerging that suggest that regions of the frontal cortex involved in inhibitory response control are directly affected by long-term exposure to drugs of abuse. The result of chronic drug use may be frontal cortical cognitive dysfunction, resulting in an inability to inhibit inappropriate unconditioned or conditioned responses elicited by drugs, by related stimuli or by internal drive states. Drug-seeking behavior may thus be due to two related phenomena: (1) augmented incentive motivational qualities of the drug and associated stimuli (due to limbic/amygdalar dysfunction) and (2) impaired inhibitory control (due to frontal cortical dysfunction). In this review, we consider the neuro-anatomical and neurochemical substrates subserving inhibitory control and motivational processes in the rodent and primate brain and their putative impact on drug seeking. The evidence for cognitive impulsivity in drug abuse associated with dysfunction of the frontostriatal system will be discussed, and an integrative hypothesis for compulsive reward-seeking in drug abuse will be presented.
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  • 114
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 146 (1999), S. 400-412 
    ISSN: 1432-2072
    Keywords: Key words Benzodiazepine ; Delay of reward ; Impulse control ; Muscimol ; pCPA ; Rat ; Serotonin ; Serotonin reuptake inhibitors ; 5-HT1A receptor ligands ; 5,7-DHT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Tolerance to delay of gratification, taken to reflect impulsiveness, has been proposed to be under the preferential control of central serotonin (5-HT) processes. Objective: The present study further examined the effects of drugs which directly or indirectly alter 5-HT transmission, on behaviour controlled by a delayed positive reinforcer. Methods: Rats were given the choice in a T-maze between two magnitudes of reward: small (two food pellets) and immediate versus large (ten pellets) but delayed. When a 15-s waiting period was imposed in the arm leading to the large reward, rats selected this arm on 65–70% of the trials. This frequency was reduced to less than 40% when the large reward was delayed by 25 s. Results: In rats whose ascending 5-HT pathways had been lesioned by infusion of 5,7-dihydroxytryptamine (5,7-DHT) into the dorsal raphe, the introduction of the 15-s delay contingency resulted in a transient larger reduction of the frequency of choice of the now-delayed reward, compared to sham operated controls. In contrast, choice behaviour of rats given 5,7-DHT into the substantia nigra did not differ from controls. para-Chlorophenylalanine (pCPA, 150 mg/kg IP, daily for 3 days), a 5-HT synthesis inhibitor, bretazenil (0.5-8 mg/kg IP), a benzodiazepine (BZD) receptor partial agonist, and muscimol (0.25-1 mg/kg IP), a GABAA receptor agonist, induced a shift toward immediate reward. In contrast to the other BZDs, alprazolam (1–2 mg/kg IP) enhanced the frequency of choice of the large-but-25 s-delayed reward. Similar increased preference for the large-but-delayed reward was induced by the selective 5-HT reuptake inhibitors, fluoxetine (4–8 mg/kg IP) and fluvoxamine (4 mg/kg IP). The full 5-HT1A receptor agonist, 8-OH-DPAT (0.015–0.5 mg/kg IP) enhanced the frequency of choice of the large reward delayed by 25 s, whereas the partial agonists, buspirone (1–4 mg/kg IP), ipsapirone (0.5–1 mg/kg IP) and MDL 73005EF (1–2 mg/kg SC), and the antagonist, WAY 100635 (4 mg/kg SC), reduced the number of choices of the large reward delayed by 15 s. Unexpectedly, WAY 100635 (2 mg/kg), which had no effect on choice whatever the delay, did not counteract the increased tolerance to delay induced by 8-OH-DPAT (0.06 mg/kg) and further reduced the frequency of choice of the large-but- 15 s-delayed reward induced by ipsapirone (0.5 mg/kg). Conclusions: These effects on tolerance to delay may be accounted for by a subtle balance between the opposing functional consequences of pre- versus post-synaptic 5-HT1A receptor activation or blockade. Overall, the present results provide further support to the idea that 5-HT processes participate in the control of impulsive-related behaviour, as assessed from tolerance to delay of reward in this particular T-maze procedure.
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  • 115
    ISSN: 1432-2072
    Keywords: Key words Ethanol ; Serotonin ; Delayed reinforcement ; Self-control ; Impulsivity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Tolerance to delay of reinforcement has been proposed as an important facet of self-control in both animals and man. Poor self-control, leading to impulsive behaviour, can be a major problem if it reaches pathological levels. Objectives: The effects of five serotonergic drugs were compared to those of ethanol on a procedure for measuring tolerance to delay of reinforcement in rats in order to elucidate further the role of the serotonin systems in the regulation of impulsive behaviour. Methods: Rats were trained to choose between a single food pellet (small reinforcer) delivered immediately or five food pellets (large reinforcer) delivered after programmed delays. At the start of each session, there was no delay between the response and delivery of the large reinforcer, but this was increased stepwise during the session to delays of 10, 20, 40 and 60 s. Results: The rats showed consistent preference for the larger reinforcer when it was not delayed but showed a shift in preference as the session continued, so that they preferred the small reinforcer when the large was delayed by 40 or 60 s. Ethanol at a dose of 1.0 g/kg produced a significance increase in preference for the small, immediate reinforcer throughout the session, although there were marked individual differences in the size of the effect. A similar, but somewhat smaller effect was seen with the 5-HT2 agonist, DOI, at a dose of 1.0 mg/kg. In contrast, the 5-HT1A agonist, 8-OH-DPAT (0.3 mg/kg) reduced preference for the large reinforcer at the start of the session, and reduced preference for the small reinforcer at the end of the session, i.e. produced a regression to indifference. Lower doses of these three drugs, and treatment with the 5-HT receptor subtype selective antagonists WAY-100635 (5-HT1A: 0.01–0.1 mg/kg), ritanserin (5-HT2: 0.1 and 0.3 mg/kg) and MDL-72222 (5-HT3: 1.0 and 3.0 mg/kg) had no significant effects on reinforcer choice. Conclusion: These data show that ethanol and DOI increase preference for the immediate reinforcer, which can be construed as evidence of an increase in impulsive behaviour (reduction in self control), whereas selective blockade of the 5-HT1A, 5-HT2 or 5-HT3 receptors using selective antagonists does not affect self-control.
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  • 116
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    Psychopharmacology 146 (1999), S. 432-439 
    ISSN: 1432-2072
    Keywords: Key words Impulsivity ; Choice ; Delay ; Methamphetamine ; Drug abuse ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Moderate doses of d-amphetamine (given both acutely and chronically) have been shown to decrease impulsivity in children with attention deficit hyperactivity disorder (ADHD) and to improve attention and learning in normal adults. In contrast, chronic doses of methamphetamine (METH) in drug abusers have been associated with increased impulsivity, and impairments in learning and attention. Objectives: We report the effects of METH on an animal model of impulsive behavior. Methods: Rats were tested using the adjusting amount (AdjAmt) procedure in which the animals choose between a delayed fixed (large) amount of water and an immediate adjusting (small) amount of water. In the acute METH study, rats were given a single dose of 0.5, 1.0, 2.0, and 4.0 mg/kg METH or saline 30 min before testing. In the chronic METH study, we determined the effects of the 4.0 mg/kg dose of METH injected chronically 1 h after behavioral testing for 14 days. Thus the rats were tested using the AdjAmt procedure 22 h after injections of METH or saline. Results: After 0.5, 1.0 and 2.0 mg/kg METH, the rats valued the delayed large rewards more than after saline, indicating that the METH decreased impulsiveness. At the 4.0 mg/kg dose, the rats failed to respond. Rats treated repeatedly with the post-session large behaviorally disruptive dose of METH valued the delayed large rewards less than the saline-treated rats, indicating that this dosing regimen of METH increased impulsiveness. Conclusions: In these experiments, the rats became less impulsive after acute non-disruptive doses of pre-session METH, whereas they became more impulsive after receiving repeated post-session injections of a dose that was behaviorally disruptive when administered acutely.
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  • 117
    ISSN: 1432-2072
    Keywords: Key words Ibogaine ; Cocaine ; Dose-response ; Locomotor activity ; Sensitization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Results of single-dose studies suggest that the effects of pretreatment with the putative anti-addictive compound, ibogaine, on drug-induced locomotor behavior depends on the previous drug history of the animal. Objectives: To compare the effects of ibogaine pretreatment on the dose-locomotor response function for cocaine in rats treated chronically with either saline or cocaine. Methods: Rats were chronically treated with either cocaine (15 mg/kg, IP, once daily for 5 days, followed by 2 week withdrawal) or saline. Ibogaine (40 mg/kg, IP) or vehicle was administered and 19 h later, a cocaine dose-locomotor response test was conducted (0, 5, 10, 20 and 40 mg/kg, IP). Results: Chronic cocaine administration augmented the locomotor response to cocaine in chronic cocaine-treated rats, compared to acutely treated controls. Ibogaine pretreatment enhanced the locomotor effects of cocaine in both chronic and acute cocaine groups. Furthermore, due to the shape of the dose-response curve, in chronic cocaine but not in acute cocaine rats, ibogaine pretreatment enhanced the locomotor response to 5 and 10 mg/kg cocaine while decreasing the locomotor response to 40 mg/kg cocaine. Conclusions: These data demonstrate definitively that ibogaine can enhance sensitivity to the locomotor stimulant effects of cocaine, an effect which depends, in part, on the previous cocaine history of the animal.
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  • 118
    ISSN: 1432-2072
    Keywords: Key words Oxytocin ; SSRIs ; Depression ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The nonapeptide oxytocin is released into systemic circulation in situations of psychosocial interaction, and has been shown to be involved in mechanisms of social bonding and social recognition in laboratory studies. In view of disturbances in psychosocial relationships being a triggering factor for depression and anxiety, it is interesting to note that experimental studies have shown oxytocin to possess antidepressant- and anxiolytic-like actions. Thus, in the present study we examined effects of the SSRI citalopram (20 mg/kg IP) on plasma oxytocin, acutely and upon repeated administration, in adult male Sprague-Dawley rats. Plasma oxytocin, and some functionally related peptides (CCK, gastrin, somatostatin and insulin), were measured by standard radioimmunoassay techniques. Acute citalopram administration produced a statistically significant increase in plasma oxytocin and CCK levels. Administration of citalopram for 14 days did not attenuate the oxytocin-releasing effect to a challenge dose of the SSRI zimeldine (20 mg/kg SC), whereas CCK levels were not increased after the subchronic citalopram treatment. Thus, the SSRI citalopram produces increased plasma oxytocin levels acutely, and there appears to be no or little tolerance to this effect upon repeated administration. There were no, or variable, effects on plasma levels of gastrin, somatostatin or insulin. It is suggested that oxytocin release is an important aspect of the pharmacological actions of SSRIs, and this could be an important contributory factor for the clinical profile of this group of antidepressants with particular efficacy in disorders of psychosocial origin.
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  • 119
    ISSN: 1432-2072
    Keywords: Key words Alcoholism ; Alcohol drinking ; Alcohol intake ; Calcium channells ; Genetic model of alcoholism ; Pharmacotherapy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Drugs which possess selective actions on a given voltage operated calcium (Ca2+) channel (VOCC) are reportedly involved in the pharmacological actions of alcohol. Recently it was shown that the 1,4-dihydropyridine (−)-BAY k 8644, an L-type VOCC agonist, reduces alcohol intake relatively selectively in the genetic drinking AA rat. This study determined whether (−)-BAY k 8644 would alter volitional alcohol drinking in two other genetic models of alcoholism, male P rats and a new strain of male and female high ethanol preferring (HEP) rats. By use of a standard 10-day preference test for water versus 3 to 30% alcohol, the maximally preferred concentration of alcohol was first determined for each rat individually, i.e. 9%, 13% or 15%. Then the rats were allowed free access over 24 h or limited access to alcohol for only 2 h, during which time the intakes of water and preferred solution of alcohol were recorded. After the drinking patterns stabilized for 4 days, saline, a solutol vehicle solution or (−)-BAY k 8644 was administered: (1) in a dose of 0.125, 0.25 or 0.5 mg/kg given intraperitoneally twice daily for 4 days during free access to alcohol; and (2) for 3 days in a dose of 0.125 or 0.25 mg/kg given subcutaneously 30 min prior to 2 h of limited access to alcohol. Fluid intakes were recorded for either 4 or 8 days after limited and free access conditions, respectively. Whereas the control solutions were without effect during 24 h access, (−)-BAY k 8644 caused a significant dose-dependent suppression of up to 80% in absolute g/kg and proportion of alcohol to total fluid consumed; this decline persisted in the post drug period. During the limited access paradigm, (−)-BAY k 8644 similarly reduced alcohol drinking maximally within the first 15 min of presentation of alcohol; again, this reduction persisted over the remaining 105 min of alcohol access. Also, individual levels of blood alcohol declined concurrently with the suppression of drinking. These results demonstrate that (−)-BAY k 8644 possesses a short latency of action on alcohol intake and that its salutary effects on drinking persist after the drug is terminated. Finally, the hypothesis that L-type calcium channel agonists may be useful as a therapeutic adjunct in the treatment of alcoholism is extended.
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  • 120
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    Psychopharmacology 142 (1999), S. 302-308 
    ISSN: 1432-2072
    Keywords: Key words Alcohol ; Beer ; Craving ; Rat ; Naloxone ; SR 141716 ; Ritanserin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were given two weeks of home cage access to either “near-beer” (a beverage that tastes like beer but contains 〈0.5% ethanol v/v) or near-beer with added ethanol (4.5% v/v), which is simply referred to as “beer”. The two groups of rats (near-beer and beer) were then trained on a “lick-based progressive ratio paradigm” in operant chambers in which an ever increasing number of licks had to be emitted for each successive fixed unit of near-beer or beer delivered. Break points (the ratio at which responding ceased) for near-beer and beer were approximately equal under baseline conditions. Rats were then tested for the effects of the 5HT2A/2C receptor antagonist ritanserin (0.625, 2.5 or 10 mg/kg), the opioid receptor antagonist naloxone (0.625, 2.5 or 10 mg/kg) or the cannabinoid CB1 receptor antagonist SR 141716 (0.3, 1 or 3 mg/kg). All three drugs caused a dose-dependent reduction of break-points and locomotor activity in both the beer and near-beer groups. However, the effects of SR 141716 and naloxone, but not ritanserin, on break-points were significantly more pronounced on rats drinking beer compared to those drinking near-beer. There were no such differential effects of any of the drugs on locomotor activity across the two groups. These results suggest that both SR 141716 and naloxone differentially affect the motivation to consume alcoholic beverages and may thus have potential as drugs for the treatment of alcohol craving.
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  • 121
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Midazolam ; Caffeine ; Cocaine ; Amphetamine ; Pentobarbitone ; Ethanol ; Drug discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Studies of the discriminative stimulus effects of drug mixtures provide an approach to polydrug abuse and studies on single drugs with multiple effects. Objective: This study was designed to investigate whether the use of the AND-OR procedure increases the specificity of drug mixture discriminations. Methods: Rats were trained to discriminate a mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND-discrimination, n = 8) or to discriminate the same mixture from its component drugs alone (AND–OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed ratio 10 schedule of food reinforcement. Results: Under AND-discrimination conditions, there was partial generalization to nicotine and midazolam when each drug was administered singly, and there was no generalization to cocaine, caffeine or ethanol. With the AND-OR discrimination, there was no generalization to any of the preceding drugs administered singly. In “single substitution” tests, nicotine or midazolam was co-administered with the training doses of pentobarbitone and amphetamine, respectively; there was full generalization in the AND-discrimination and partial generalization under AND-OR conditions. Cocaine co-administered with pentobarbitone generalized fully under both procedures, but the dose of cocaine needed was much larger in the AND-OR than in the AND-discrimination. In “dual substitution” tests, mixtures of two novel substances were tested. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. Throughout the studies, in every instance where comparisons were made, generalization was greater or occurred at lower doses under AND- than under the AND-OR discrimination. Conclusions: The study yielded extensive evidence supporting the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on drug mixtures.
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  • 122
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Mecamylamine ; Tolerance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Chronic injections of nicotine in rats produce upregulation of nicotinic cholinergic receptors. It has been proposed that this upregulation is a reflection of receptor desensitization and is the basis of functional tolerance. Mecamylamine, a non-competitive antagonist that blocks activation of nicotinic receptors, does not prevent upregulation produced by nicotine injections. This suggests that receptor activation is not a prerequisite for nicotine-induced receptor upregulation. Therefore, the present experiments tested whether mecamylamine would also fail to prevent the development of tolerance to nicotine. Six daily pairings of mecamylamine (1 mg/kg SC) with nicotine did block the development of tolerance to nicotine-induced antinociception (0.35 mg/kg) and to the ability of nicotine to suppress milk intake (0.66 mg/kg). In another experiment, six daily injections of mecamylamine, when given alone, did not alter the effects of a subsequent, acute injection of nicotine (0.35 mg/kg) in inducing antinociception in rats. There was no evidence that after six pairings of mecamylamine with nicotine, the cues associated with mecamylamine delivery took on conditioned antagonistic properties. These findings suggest that, unlike the receptor upregulation that results from either continuous or repeated nicotine administration, the tolerance following a short series of intermittent nicotine injections is dependent on receptor activation.
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  • 123
    ISSN: 1432-2072
    Keywords: Key words Amphetamine ; Behavioral sensitization ; MK-801 ; NMDA receptor ; State-dependency ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Many laboratories have reported that coadministration of N-methyl-d-aspartate (NMDA) receptor antagonists with psychomotor stimulants prevents the development of behavioral sensitization and therefore concluded that NMDA receptor transmission is necessary for sensitization. According to an alternative ”state-dependency” interpretation, NMDA receptor antagonists do not prevent sensitization. Rather, they become a conditioned stimulus for the sensitized response, i.e., it is only elicited in response to combined administration of the NMDA receptor antagonist and the stimulant. This hypothesis is supported by progressive augmentation of the locomotor response to the drug combination during the induction phase, and expression of sensitization when challenged with the combination but not the stimulant alone. To test this hypothesis, rats were treated during a 6-day induction phase with amphetamine (Amph) alone or in combination with the competitive NMDA receptor antagonist CGS 19755 (10 mg/kg) or the non-competitive NMDA receptor antagonist MK-801 (0.05, 0.1 and 0.25 mg/kg). When CGS 19755 was coadministered with Amph, there was no progressive augmentation of response to the drug combination. When challenged with Amph alone, rats did not exhibit the biphasic pattern of locomotor activity characteristic of Amph sensitization. No sensitization of stereotyped behaviors was evident, although the ambulatory response was greater than that exhibited by naive rats. Results with MK-801 were complex, but progressive augmentation of response to the drug combination appeared to in part reflect sensitization to MK-801 and could be dissociated from the ability of MK-801 to prevent the development of sensitization as assessed by response to challenge with Amph alone. Many of these findings are inconsistent with predictions of the ”state-dependency” hypothesis. Moreover, the ability of NMDA receptor antagonists to prevent biochemical and electrophysiological correlates of sensitization is difficult to reconcile with the idea that sensitization develops in the presence of NMDA receptor blockade but cannot be expressed. Together, these findings suggest that the ability of NMDA receptor antagonists to prevent Amph sensitization reflects a requirement for NMDA receptor transmission during its induction.
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  • 124
    ISSN: 1432-2072
    Keywords: Key words SSRI ; Cytochrome P450 ; Serotonin ; Microdialysis ; Norfluoxetine ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Amphetamine stimulates locomotor activity, in large part by activating central dopaminergic systems. Serotonin shares on overlapping distribution with dopamine and has been shown to modulate dopaminergic function and dopamine-mediated behaviors. The present study examined whether increasing serotonergic function, via the selective serotonin reuptake inhibitor fluoxetine, would alter the stimulatory effects of amphetamine on locomotor activity and dopamine overflow in the nucleus accumbens. In addition, the present study determined whether fluoxetine treatment would alter the metabolism of amphetamine. Results show that 5.0 mg/kg fluoxetine potentiated the locomotor activity induced by amphetamine (0.5–1.0 mg/ kg), and enhanced the increased dopamine overflow in the nucleus accumbens induced by amphetamine. Fluoxetine treatment also resulted in a higher concentration of amphetamine in the CNS. Together, these findings indicate that acute fluoxetine treatment potentiates the locomotor stimulating and dopamine activating effects of amphetamine. Further, the results indicate that fluoxetine potentiates the effects of amphetamine by decreasing the metabolism of amphetamine, probably through inhibition of cytochrome P450 isozymes.
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  • 125
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    Psychopharmacology 144 (1999), S. 77-82 
    ISSN: 1432-2072
    Keywords: Key words Acquisition ; Cocaine ; Heroin ; Rat ; Self-administration ; Sex difference
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Despite numerous reports that male and female animals differ in behavioral responses to drugs, few studies have investigated sex differences in drug-reinforced behavior. Objectives: Acquisition of IV cocaine and heroin self-administration was compared in 20 female and 22 male Wistar rats. Methods: An autoshaping procedure was used to train rats to press a lever that resulted in either a 0.2 mg/kg infusion of cocaine or a 0.015 mg/kg infusion of heroin under a fixed-ratio 1 (FR 1) schedule. Daily sessions consisted of six 1-h autoshaping components followed by a 6-h self-administration component. During each autoshaping component, a retractable lever briefly (15 s) extended into the test chamber on a random interval schedule with a mean of either 90 s (cocaine groups) or 480 s (heroin groups) and either ten (cocaine groups) or five (heroin groups) computer-automated infusions were delivered each hour. During each 6-h self-administration component, the lever remained extended and each response on the lever resulted in an infusion of either cocaine (0.2 mg/kg) or heroin (0.015 mg/kg). The criterion for acquisition of cocaine self-administration was a mean of at least 100 infusions and the criterion for heroin self-administration was a mean of at least 20 infusions during the self-administration component over five consecutive sessions. Results: Female rats acquired both cocaine and heroin self-administration more rapidly than males. Acquisition of cocaine self-administration occurred in a greater percentage of female rats compared to males. Female rats self-administered more cocaine than males after acquisition criteria had been met. Conclusions: These findings indicate that female rats were more vulnerable than males to the acquisition of cocaine and heroin self-administration under the conditions of the present experiment.
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  • 126
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    Psychopharmacology 144 (1999), S. 111-120 
    ISSN: 1432-2072
    Keywords: Key words Heroin ; Self-administration ; Dependence ; Naloxone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Non-dependent and dependent opiate users appear to be driven by two distinct motivational factors: the primary reinforcing properties of the drug, and the negative reinforcing effects associated with relieving the negative affective component of opiate withdrawal in the dependent state. Objective: To investigate the motivational significance of opioid dependence on heroin self-administration (HSA) in rodents. Methods: Rats were trained to self-administer heroin intravenously (0.06 mg/kg per infusion; FR1), and opiate dependence was induced by subcutaneous implantation of two morphine (75 mg base) pellets.Rats in a non-dependent control group received placebo pellets. Three days after pellet implantation, HSA was resumed in daily 3-h sessions until baseline criteria were met and testing was conducted with subcutaneous injections of vehicle or naloxone (0, 0.003, 0.01, 0.03 mg/kg) 115 min into the session. Results: Morphine-dependent rats significantly increased HSA upon 0.01 mg/kg naloxone treatment, but decreased response rates at 0.03 mg/kg. Placebo pellet-implanted rats increased heroin intake at the 0.01 and 0.03 mg/kg doses. In a second experiment, the HSA session was shortened to 1 h and the training dose reduced to 0.03 mg/kg per infusion in new groups of animals. HSA in placebo pellet-implanted rats was increased only following the highest dose of the antagonist, while dependent rats were still affected by naloxone doses of 0.003–0.03 mg/kg. When subjected to a progressive-ratio schedule (experiment 3), breaking point values in dependent animals were 198% above baseline. Conclusions: The present study supports the hypothesis that dependence-induction by morphine-pellet implant in rats resulted in increased sensitivity to very small naloxone doses, as measured by changes in HSA. Taken together, these data suggest that opiate dependence, as measured by changes in sensitivity to naloxone, is a continuum which can contribute to the motivational state of drug-seeking.
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  • 127
    ISSN: 1432-2072
    Keywords: Key words Schizophrenia ; Extrapyramidal side-effect ; Neuroleptic ; Antipsychotic ; Dopamine D2 receptor ; Serotonin 5-HT1A receptor ; Intrinsic activity ; Paw test ; Catalepsy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Combining neuroleptics with 5-HT1A ligands is thought to improve the preclinical profile of neuroleptics and may be of interest in the development of new compounds that have greater therapeutic potential and/or are better tolerated. Objective: To examine 1) the ability of 5-HT1A ligands to alter the effects of neuroleptics in preclinical models for antipsychotic potential (hindlimb retraction time in the paw test) and extrapyramidal side-effects (forelimb retraction time in the paw test; catalepsy tests), 2) the role of intrinsic activity at 5-HT1A receptors in the modulatory effects of 5-HT1A ligands, and 3) the generality of the interactions across neuroleptics. Methods: The effects of different doses of 5-HT1A ligands with intrinsic activity ranging from high (e.g., 8-OH-DPAT) to low (e.g., WAY 100135) administered together with a fixed, high dose of the neuroleptics haloperidol, risperidone, and tropapride were examined in the paw test and on catalepsy. Results: Firstly, the 5-HT1A agonists 8-OH-DPAT and ipsapirone attenuated the extrapyramidal-like effects of haloperidol and risperidone more than their therapeutic-like effects; this was not observed for tropapride, where all of its effects were markedly attenuated. Secondly, neither the weak 5-HT1A agonist WAY 100135 nor the silent antagonist WAY 100635 attenuated the effects of neuroleptics. Thirdly, neuroleptics apparently differed in their sensitivity to interactions with 5-HT1A agonists inasmuch as 8-OH-DPAT and ipsapirone attenuated the effects of tropapride on hindlimb retraction times more than those of haloperidol or risperidone. Conclusions: The present data suggest that 5-HT1A agonists with intermediate or high, but not low, intrinsic activity may abolish the extrapyramidal effects of neuroleptics. Together with results of previous studies, it appears that 5-HT1A agonists alter the antipsychotic-like effects of neuroleptics, although this may depend on the neuroleptic studied.
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  • 128
    ISSN: 1432-2072
    Keywords: Key words Delayed non-matching to position task ; Scopolamine ; ENA 713 ; Exelon ; Working memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: The disruption of working memory in the delayed non-matching to position (DNMTP) task by the muscarinic antagonist, scopolamine, is considered to be a model of the spatial working memory deficit in Alzheimer’s disease (AD) patients. Objective: To investigate whether ENA 713 (Exelon) (0.1, 0.5 mg/kg, IP), an acetylcholinesterase inhibitor, would reverse the effects of scopolamine in the DNMTP task. Methods: Male Lister Hooded rats were trained to criterion in an operant DNMTP task (0- to 16-s delay intervals) before receiving vehicle, scopolamine (0.05 mg/kg, SC) alone, ENA 713 (0.1, 0.5 mg/kg, IP) alone, or combinations of scopolamine and ENA 713, in two variations of the task – with and without barriers inserted between the food magazine and the two levers. Barriers were inserted to prevent the use of positional strategies to perform the task, since this behaviour may confound the conclusions of the effect of drugs on working memory. Results: It was found that: (i) scopolamine significantly reduced choice accuracy delay-dependently in both test situations while modifying non-mnemonic measures of task performance delay-independently, indicating an impairment of working memory; (ii) ENA 713 (0.5 mg/kg) significantly attenuated the scopolamine-induced impairment of working memory and significantly reduced the scopolamine-induced changes in some non-mnemonic measures of task performance; (iii) the presence of barriers did not alter the effects of scopolamine and ENA 713 on working memory. Conclusion: ENA 713 reversed the working memory deficit induced by scopolamine. These results are consistent with the attenuation of learning and memory disruptions due to cholinergic dysfunction by ENA 713 in other preclinical assays, and predict a drug-induced improvement in working memory in AD patients.
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  • 129
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    Psychopharmacology 146 (1999), S. 19-23 
    ISSN: 1432-2072
    Keywords: Key words Serotonin ; Sensitization ; Rat ; Dopamine opiate ; Movement disorder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Repeated high doses of morphine in the rat cause stereotypic gnawing behavior that can be re-expressed by a low dose of morphine weeks and even months after the initial treatment. The determination of the role of serotonin in this sensitized morphine-induced behavior has both empirical and theoretical relevance. Objectives: To determine whether the serotonin-reuptake blocker fluoxetine will block the development and/or the expression of this opiate-induced stereotypy. Methods: Rats were given four 10-mg/kg injections of morphine alone or with 5.0 mg/kg fluoxetine over a 36-h period. At weekly intervals for 6 weeks after the last of the sensitizing morphine doses, all rats were challenged with 4.0 mg/kg morphine. At week 2 and week 4, however, the morphine was co-administered with fluoxetine. Results: Fluoxetine completely blocked the expression of the morphine-induced stereotypy; however, when the morphine/fluoxetine-treated rats were challenged with morphine alone, they expressed similar degrees of stereotypy as the rats that initially only received morphine. Conclusions: The results indicate that increasing synaptic serotonin will block the expression but not the development of sensitization to the oral stereotypic effects of repeated high doses of morphine. Also, despite the complete blocking of the morphine effect by fluoxetine during the sensitization phase, the presence of significant biting by these rats during the challenge with morphine alone argues that conditioning factors are not a necessary component for the morphine sensitization to develop.
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  • 130
    ISSN: 1432-2072
    Keywords: Key words Dextromethorphan ; Dextrorphan ; Phencyclidine ; Self-administration ; Drug discrimination ; Monkey ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Dextromethorphan (DXM) and its metabolite, dextrorphan (DXO) have neuroprotective and anticonvulsant properties through their activity as N-methyl-d-aspartate (NMDA) receptor channel blockers. Based on this receptor activity, coupled with reports of DXM abuse, both were evaluated for abuse potential and phencyclidine (PCP)-like behavioral effects in two animal models. Objectives and methods: The discriminative stimulus properties of DXO and DXM were tested in rats (3–56 mg/kg DXM, i.p. and 2.2–40.9 mg/kg DXO, i.p.) and rhesus monkeys (0.3–10 mg/kg DXM, i.m. and 0.25–8.0 mg/kg DXO, i.m.) trained to discriminate PCP from saline using a standard two-lever drug-discrimination paradigm under a fixed-ratio (FR) schedule of food reinforcement. In a second set of experiments, i.v. self-administration of DXO (10–100 µg/kg/infusion) and DXM (10–1000 µg/kg/infusion) were tested under a FR schedule of reinforcement in monkeys trained to lever press for infusions of PCP during daily 1-h sessions. Results: In rats, both DXM and DXO produced a dose-dependent substitution for PCP. When tested in monkeys, DXM yielded partial (1 monkey) and full (2 monkeys) substitution for PCP, while DXO substituted fully for PCP in all four subjects tested. In the self-administration study, in five of the six subjects, at least one dose of DXM served as a positive reinforcer, maintaining infusion rates above those for saline. For DXO, at least one dose maintained infusion numbers well above mean saline infusion numbers in all subjects. Conclusions: Taken together, these data show that DXM has some PCP-like effects in rats and monkeys, but that they are more reliably produced by its metabolite, DXO. Thus, high doses of DXM may have some PCP-like abuse potential in humans but this potential may be associated with, or enhanced by, metabolism of DXM to DXO.
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  • 131
    ISSN: 1432-2072
    Keywords: Key words Amphetamine ; Fluoxetine ; Intracranial self-stimulation thresholds ; Withdrawal ; Depression ; Selective serotonin reuptake inhibitors ; Psychostimulant ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Withdrawal from chronic amphetamine administration is characterized by deficits in reward that resemble some symptoms of depression. Nevertheless, the effects of long-term administration and withdrawal from other drugs, such as fluoxetine, that have the potential to elevate mood in depressed individuals have not been characterized. Objectives: The purpose of this study was to characterize the effects of withdrawal from chronic amphetamine or fluoxetine administration on central reward function. Furthermore, the effects of acute or chronic pretreatment with fluoxetine on responsiveness to an acute amphetamine challenge were examined to identify potential interactions between the two drugs. Methods: A rate-independent discrete-trial threshold procedure was used to characterize self-stimulation behavior in rats prepared with bipolar electrodes in the medial forebrain bundle. Results: Elevations in intracranial self-stimulation (ICSS) thresholds, reflecting a decrease in the reward value of the stimulation, were associated with withdrawal from various chronic amphetamine treatment regimens (1–5 mg/kg, three injections per day for 1, 2, 4 or 6 days). The magnitude and duration of threshold elevations were proportional to the duration and dose of amphetamine treatment prior to withdrawal. In contrast, no alterations in ICSS thresholds were associated with withdrawal from chronic fluoxetine treatment (5 mg/kg/day for 15 days). While neither acute nor chronic administration of fluoxetine alone altered ICSS thresholds, chronic pretreatment with fluoxetine blocked the threshold-lowering effect of acute amphetamine administration (4 mg/kg), but acute pretreatment did not. Amphetamine-induced decreases in response latency, a measure of motor performance, were not affected by either chronic or acute fluoxetine pretreatment. Conclusions: The results of these experiments suggest that chronic fluoxetine treatment may induce adaptive changes in serotonergic transmission that, in themselves, do not alter the function of central reward processes, but may alter the ability of amphetamine to potentiate ICSS reward. In addition, the lack of change in ICSS thresholds during withdrawal from the chronic fluoxetine treatment regimen used suggests that withdrawal from all mood-altering drugs may not necessarily produce changes in central reward functions.
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  • 132
    ISSN: 1432-2072
    Keywords: Key words Ethanol ; Initiation ; Sucrose-substitution ; Appetitive-consummatory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The concepts of appetitive and consummatory behaviors provide a framework for examining ethanol-drinking behavior. However, traditional studies of ethanol self-administration using dipper procedures make separating the appetitive from the consummatory components difficult. Objective: This study compared the ability to initiate ethanol self-administration using a new sipper-tube self-administration procedure with the older established sucrose-substitution initiation model that employed dipper presented reinforcement. The new model was developed to allow for an assessment of the appetitive and consummatory components in ethanol self-administration. Methods: For the sipper-tube procedure, the rats were initiated to self-administer ethanol using a sucrose-substitution procedure that provided limited access to a sipper tube containing ethanol. This procedure required the completion of a fixed ratio requirement (FR4) in order to gain access to a sipper tube for 20 min. Initially, a 20% sucrose solution with no ethanol was provided in the sipper tube. Over sessions, the concentration of sucrose was reduced and the ethanol concentration increased, until 10% ethanol in water was the solution presented. A second group of animals was initiated to self-administer ethanol using the dipper-presentation procedure employed in our laboratory for many years. This group was used for comparison of the effectiveness of initiation in the sipper-tube procedure. Results: Following initiation, the sipper-tube rats self-administered 10% ethanol in water with intakes averaging 0.75 g/kg during the 20-min drinking period. Increasing the ethanol concentrations as high as 20%, increased intakes as high as 1.5 g/kg. The ethanol intakes observed were similar to those obtained with the dipper initiation procedure but occurred in one-third of the time. Conclusions: The sipper-tube procedure employed here results in similar ethanol self-administration behavior as has been found with a dipper presentation procedure. More importantly, however, it allows for a separation of the appetitive and consummatory components of ethanol self-administration. This separation may prove useful for examining the strength of ethanol-seeking behaviors without the confound of increasing levels of ethanol interacting with the appetitive seeking behaviors.
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  • 133
    ISSN: 1432-2072
    Keywords: Key words Deramciclane ; Ritanserin ; Chlordiazepoxide ; Slow wave sleep ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of serotonergic and benzodiazepine type anxiolytic drugs on the cortical activation and sleep-wakefulness cycle were compared by evaluating the effects of ritanserin and deramciclane (EGIS-3886), two 5-HT2 receptor antagonists, and chlordiazepoxide on the electroencephalogram (EEG) in freely moving rats. Following drug administration (1, 3, and 10 mg/kg, PO for all drugs), EEG was continuously sampled for 6 h and power spectra were calculated for every 5 s to assess changes in slow wave activity and sleep phases. In a separate test, anticonvulsant effects of the drugs were examined in mice. Both deramciclane and ritanserin slightly increased total time spent in deep sleep (DS) and lengthened sleep episodes. In contrast, chlordiazepoxide had a strong inhibitory action on DS, sleep time being shifted to more superficial light sleep (LS). The incidence and length of the high voltage spindle (HVS) episodes characteristic for the motionless, awake rat were increased at the highest dose of both deramciclane and ritanserin, while it was decreased by chlordiazepoxide. In mice, chlordiazepoxide had a marked anticonvulsant effect, while deramciclane was moderately effective and ritanserin ineffective. In conclusion, the 5-HT2 receptor antagonist anxiolytic drugs seem to be superior compared to the benzodiazepine type anxiolytic drug, chlordiazepoxide, as ritanserin and deramciclane improved sleep quality by increasing sleep episode length and time spent in DS, while chlordiazepoxide enhanced sleep fragmentation and decreased DS.
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  • 134
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    Psychopharmacology 142 (1999), S. 327-333 
    ISSN: 1432-2072
    Keywords: Key words Caffeine ; Nicotine self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The prevalence of tobacco smoking and coffee drinking place nicotine and caffeine among the most used licit drugs in many societies and their consumption is often characterised by concurrent use. The pharmacological basis for any putative interaction between these drugs remains unclear. Epidemiological reports support anecdotal evidence, which suggests that smokers consume caffeine to enhance the euphoric effects of nicotine. The aim of the present experiment was to examine effects of chronic exposure to caffeine on responding maintained by nicotine. Sprague-Dawley rats consuming caffeine (approximately 150–180 mg/kg per day) in their drinking water for 7 days prior to the beginning and throughout behavioural testing acquired intravenous nicotine self-administration (0.03 mg/kg per infusion) more rapidly than did controls. In a cross-over design, exclusion of caffeine brought levels of nicotine self-administration back to baseline, while adding caffeine to the drinking water of control rats increased responding maintained by nicotine over 90%. These findings strongly suggest that caffeine can potentiate the reinforcing properties of nicotine, thus highlighting the importance of environmental factors in shaping and maintaining tobacco smoking.
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  • 135
    ISSN: 1432-2072
    Keywords: Key words Continuous cocaine ; Tolerance ; 5-HT3 receptor ; DA release ; Nucleus accumbens ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously reported that continuous cocaine administration functionally down regulates 5-HT3 receptors in the nucleus accumbens. The current experiments evaluated the duration of behavioral tolerance to cocaine and whether the duration of behavioral tolerance and 5-HT3 receptor down-regulation co-varied. Rats were withdrawn from a pretreatment regimen (40 mg/kg/per day cocaine or 0.9% saline for 14 days) for 1, 7 or 14 days. The rats were either sacrificed, and slices from the nucleus accumbens obtained, or were exposed to behavioral rating procedures. The results indicated that continuous cocaine administration significantly attenuated the ability of mCPBG to facilitate K+-stimulated DA release on days 1 and 7, but not day 14, of withdrawal. Furthermore, continuous cocaine administration induced behavioral tolerance to a cocaine challenge on days 1 and 7, but not day 14, of withdrawal. These results suggest that continuous cocaine administration functionally down-regulates 5-HT3 receptors in the nucleus accumbens, and this functional down-regulation co-varies with the behavioral tolerance induced by continuous cocaine administration. Hence, a functional down-regulation of accumbens 5-HT3 receptors may represent a partial mechanism for the tolerance following continuous cocaine administration.
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  • 136
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    Psychopharmacology 142 (1999), S. 369-374 
    ISSN: 1432-2072
    Keywords: Key words Clozapine ; Withdrawal ; Dependence ; Temperature ; Atypical antipsychotic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: In schizophrenics, clozapine has been reported to induce various withdrawal signs and rapid onset relapse to psychosis on cessation of chronic treatment. Objective: The study was designed to develop an animal model of one aspect of clozapine tolerance and withdrawal using core body temperature measures. Methods: Two groups of 15 female Wistar rats were treated chronically (b.i.d.) with clozapine at 6 or 12 mg/kg per injection for 21 days prior to cessation of drug treatment, withdrawal being studied over 4 consecutive days. Body temperatures were assessed daily throughout the study. Results: Acutely, clozapine induced dose-related hypothermia, to which complete tolerance developed in both groups, the development of tolerance being more rapid in the group treated with 6 mg/kg per injection of clozapine. During withdrawal only the group treated chronically with 12 mg/kg per injection of clozapine showed rapid onset significant hyperthermia. This dissipated progressively over days, and was completely absent after 4 days of withdrawal. Conclusions: Clozapine induced a clear somatic withdrawal sign after chronic treatment. It is suggested that, in future research in both humans and animals, it is important to attempt to differentiate between clozapine withdrawal and clozapine withdrawal-induced relapse to psychosis. It is also important to characterise the clozapine withdrawal syndrome fully in animals; to establish the neurochemical mechanisms involved in such withdrawal; and to determine which novel antipsychotics are most efficacious in inducing clozapine-like withdrawal effects, in suppressing clozapine withdrawal, and in preventing relapse to psychosis in patients being transferred from clozapine to novel atypical antipsychotic drugs.
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  • 137
    ISSN: 1432-2072
    Keywords: Key words Antinociception ; Butorphanol ; Relative efficacy ; Opioid ; Rat ; Stimulus intensity ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: A common treatment strategy for the management of severe pain involves the co-administration of multiple opioid analgesics. Due to the increasing popularity of this practice, it is becoming increasingly important to understand the interactions between clinically employed opioids under a wide range of conditions. Objective: The purpose of the present investigation was to examine the effects of opioid combinations following acute and chronic administration of the low-efficacy mu-opioid butorphanol, and to determine if the effects of these combinations are modulated by the intensity of the nociceptive stimulus. Methods: In a warm-water, tail-withdrawal procedure, rats were restrained and the latencies to remove their tails from 50°C (low temperature) and 55°C (high temperature) water were measured following both acute and chronic administration of butorphanol. Opioids possessing both high (etorphine, levorphanol, morphine) and low [dezocine, (–)-pentazocine, nalbuphine] relative efficacy at the mu receptor were examined. Results: Under acute conditions, etorphine, levorphanol, morphine and dezocine increased tail-withdrawal latencies at both low and high temperatures, whereas (–)-pentazocine, nalbuphine and butorphanol increased latencies only at the low temperature. A dose of 30 mg/kg butorphanol increased the effects produced by these opioids at the low temperature, but antagonized the effects of etorphine, levorphanol, morphine and dezocine at the high temperature. During chronic treatment with 30 mg/kg per day butorphanol, tolerance was conferred to the antinociceptive effects of all the opioids examined, with greater degrees of tolerance conferred to those opioids possessing low efficacy at the mu receptor. During butorphanol treatment, etorphine, levorphanol and morphine increased tail-withdrawal latencies at both water temperatures, dezocine increased latencies at only the low temperature, and (–)-pentazocine, nalbuphine and butorphanol failed to increase latencies at either temperature. A dose of 30 mg/kg butorphanol antagonized the antinociceptive effects of etorphine, levorphanol, morphine and dezocine during chronic treatment, and these effects were observed at both water temperatures. Conclusions: These findings indicate that the interactions between butorphanol and other mu opioids vary quantitatively between low and high stimulus intensities, and between acute and chronic conditions. In most instances, however, these interactions can be predicted from the effects of the drugs when administered alone.
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  • 138
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    Psychopharmacology 143 (1999), S. 293-301 
    ISSN: 1432-2072
    Keywords: Key words Methamphetamine ; Drug discrimination ; Norepinephrine ; Desipramine ; Nisoxetine ; Isoproterenol ; Propranolol ; Methoxamine ; Prazosin ; Clonidine ; Yohimbine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale:Neurochemical and clinical studies indicate involvement of noradrenergic (NE) neurotransmitter system in the actions of methamphetamine. Objective:The present study investigated NE involvement in the discriminative-stimulus effects of methamphetamine. Methods:In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine, IP, from saline under a fixed-ratio schedule of food presentation, effects of various NE agonists, antagonists and uptake inhibitors were tested. Results: Desipramine (3.0–18.0 mg/kg) and nisoxetine (5.6–30.0 mg/kg), two selective NE-uptake inhibitors, did not significantly generalize to methamphetamine when administered alone, but 5.6 mg/kg desipramine and 10.0 mg/kg nisoxetine significantly shifted the methamphetamine dose-response curve to the left. The beta NE agonist, isoproterenol (0.56–3.0 mg/kg), and antagonist, propranolol (1.0–18.0 mg/kg), neither generalized to methamphetamine when given alone nor altered the discriminative-stimulus effects of methamphetamine when administered in combination. The alpha-1 NE agonist methoxamine (1.0–5.6 mg/kg) failed to generalize to the methamphetamine training stimulus. When given in combination with methamphetamine, the alpha-1 NE antagonist, prazosin (1.0 mg/kg), shifted the methamphetamine dose-response curve somewhat to the right and partially blocked the discriminative-stimulus effects of the 1.0 mg/kg training dose of methamphetamine, but these changes were not significant or dose-related, with further increases in prazosin dose (1.8–10.0 mg/kg) either producing similar or smaller changes. The alpha-2 NE agonist, clonidine, partially generalized to methamphetamine at doses of 0.1–0.18 mg/kg and increased drug-appropriate responding at lower doses of methamphetamine, but it partially blocked the discriminative-stimulus effects of higher 0.56–1.0 mg/kg doses of methamphetamine over the same dose range. The alpha-2 NE antagonist, yohimbine, also partially generalized to methamphetamine and blocked the discriminative-stimulus effects of the 1.0 mg/kg training dose of methamphetamine at doses of 5.6–10.0 mg/kg. A lower 3.0 mg/kg dose of yohimbine increased methamphetamine-appropriate responding when given together with low 0.1–0.3 mg/kg doses of methamphetamine. Conclusions:The present data suggest that the NE system plays a modulatory role in the discriminative-stimulus effects of methamphetamine. These effects appear to be mediated through NE uptake sites and alpha-2 receptors, with limited involvement of alpha-1 receptors and beta receptors.
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    Psychopharmacology 143 (1999), S. 315-317 
    ISSN: 1432-2072
    Keywords: Key words SR141716 ; Hyperphagia ; Rat ; Pre-feed ; Eating ; Appetite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Central cannabinoid systems have been implicated in appetite regulation by the respective hyperphagic actions of exogenous cannabinoids, such as Δ9-THC, and hypophagic effects of selective cannabinoid receptor antagonists. Objective: This study examined whether an endogenous cannabinoid, anandamide, could induce overeating, via a specific action at central (CB1) cannabinoid receptors. Methods: Pre-satiated male rats (n=18), received subcutaneous injections of anandamide (0.5, 1.0, 5.0, 10.0 mg/kg) before 3-h, nocturnal food intake tests. In a second series of intake tests (n=8), anandamide injection (1.0 mg/kg) was preceded by injection of the specific CB1 receptor antagonist, SR141716 (0.1, 0.5, 1.0 mg/kg SC). Results: All doses of anandamide induced significant overeating, with 1.0 mg/kg being most potent. Additionally, hyperphagia induced by 1.0 mg/kg anandamide was dose-dependently attenuated by SR141716 pretreatment. Conclusion: This first demonstration of anandamide-induced, CB1-mediated, overeating provides important evidence for the involvement of a central cannabinoid system in the normal control of eating.
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  • 140
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    Keywords: Key words Methamphetamine ; Dopamine ; Serotonin ; Phentermine ; Fenfluramine ; Drug-discrimination ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To analyze the involvement of dopamine (DA) and serotonin (5-HT) release in the stimulus properties of methamphetamine, two amphetamine analogs that selectively release either brain DA (phentermine) or 5-HT (fenfluramine) were tested for their ability to substitute for methamphetamine in rats discriminating methamphetamine (1.0 mg/kg) from saline. They were subsequently tested for their ability to alter IV methamphetamine (0.06 mg/kg per injection) self-administration in the same species when given as a pretreatment. The DA releaser phentermine, like methamphetamine itself, decreased methamphetamine self-administration (to 70% of baseline responding), but only at a dose of 3.0 mg/kg that fully generalized to the methamphetamine stimulus in the discrimination study. The 5-HT releaser fenfluramine attenuated methamphetamine self-administration to a much larger extent than phentermine (to 37% of baseline responding) at a dose of 1.8 mg/kg that did not generalize to methamphetamine and did not decrease rate of responding in the discrimination study. Tolerance developed to the inhibitory effect of 1.8 mg/kg fenfluramine on methamphetamine self-administration when it was given repeatedly over four consecutive daily sessions. The fenfluramine-induced decrease in methamphetamine self-administration was also attenuated when it was given together with the small 1.0 mg/kg dose of phentermine. These results suggest that DA release plays a dominant role in the discriminative stimulus effects of methamphetamine. However, stimulation of 5-HT release can strongly modify methamphetamine self-administration.
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  • 141
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Prepulse inhibition ; Sensorimotor gating ; Schizophrenia ; Medial geniculate body ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prepulse inhibition of acoustic startle is the normal reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Previous studies have shown that several neuroanatomical structures and pathways in the brain are involved in the modulation of prepulse inhibition. In the present study, the functional importance of the medial geniculate body (MG) in the modulation of prepulse inhibition was investigated. To this end, in vivo brain microdialysis probes were used to infuse drugs locally into the MG of awake, freely moving rats simultaneously with startle response and prepulse inhibition measurements in the same animals. Intrageniculate infusion of the sodium channel blocker, tetrodotoxin, significantly reduced prepulse inhibition without affecting baseline startle amplitude. A similar effect was obtained after intrageniculate infusion of the GABAB receptor agonist, baclofen. In addition, intrageniculate infusion of muscimol, an agonist at the GABAA receptor complex, reduced prepulse inhibition, although this effect was obtained at a higher concentration of the drug compared to that of baclofen. These studies suggest that the MG is involved in the modulation of prepulse inhibition and that auditory signals relayed via the MG may be subjected to inhibitory control at this level, involving GABA neurotransmission.
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  • 142
    ISSN: 1432-2072
    Keywords: Key words Nicotinic acetylcholine receptor ; ABT-418 ; Methylphenidate ; Basal forebrain ; 192 IgG-saporin ; Sustained attention ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Loss of telencephalic cholinergic projections has been postulated to contribute significantly to the cognitive decline associated with aging and dementia. Objective: The effects of the nicotinic acetylcholine receptor agonist ABT-418, a potential therapeutic drug for the treatment of the age- and dementia-associated cognitive disorders, were tested in an animal model of the cortical cholinergic deafferentation-induced impairments in sustained attention. Methods: Animals were trained in an operant task designed to test sustained attention performance. A partial loss of cortical cholinergic inputs was produced by infusions of 192 IgG-saporin into the basal forebrain. The effects of the systemic administration of ABT-418 (0.04, 0.13, 0.39 mg/kg) and the psychostimulant methylphenidate (0.2, 0.4, 0.8 mg/kg) were assessed. Results: Compared with sham-lesioned animals, this lesion resulted in a decrease in the relative number of hits while the relative number of correct rejections remained unaffected. Administration of ABT-418 significantly improved the relative number of hits. Furthermore, this effect of ABT-418 interacted with the effects of the lesion. Unexpectedly, this interaction was based on a significant enhancement of the performance of sham-lesioned animals while no effects were found in 192 IgG-saporin-lesioned animals. Administration of methylphenidate did not affect performance. Conclusions: While these data do not support the hypothesis that administration of ABT-418 attenuates the impairments in attentional performance that result from loss of cortical cholinergic inputs, they support previous notions about this drug’s ability to enhance cognitive processes in intact subjects.
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  • 143
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    Psychopharmacology 144 (1999), S. 213-219 
    ISSN: 1432-2072
    Keywords: Key words Alcohol ; Self-administration ; Animal model ; Behavioral economics ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: For the purpose of investigating the determinants of preference for alcohol, it would be advantageous to use a procedure in which the subjects had concurrent access to alcohol and an isocaloric food. However, in widely used animal models, the introduction of a weak sucrose solution markedly reduced alcohol consumption. In contrast, when alcohol was sweetened, rats defended high baseline levels of alcohol intake despite access to chow, 10% sucrose, and increases in body weight that markedly reduced food consumption. Under these conditions, certain pharmacological treatments selectively reduced alcohol consumption. The present experiment further tests the generality of the contrast between food and sweetened alcohol consumption in rats. Objective: To test if rats will defend baseline levels of alcohol consumption when (1) the competing reinforcer is an isocaloric, preferred food and (2) when the cost of defending alcohol entails a decrease in food consumption as well as an increase in response output. Methods: The rats had access to a 10% alcohol plus 0.25% saccharin solution and an isocaloric, 14.8% Polycose solution in a two-lever, choice procedure. In the initial condition, the response requirement for each drink was set at five responses (variable-ratio 5); in subsequent conditions the variable-ratio values were increased to 7.5, 10, 15, and 30 responses. Results: In the initial condition, the rats drank twice as much Polycose as alcohol. However, with increases in the variable-ratio requirements, Polycose consumption systematically decreased, whereas sweetened alcohol consumption remained at its baseline level or above in all but the variable-ratio 30 condition. Conclusions: Rats defended baseline alcohol consumption but not baseline food consumption. As alcohol and food consumption can be dissociated in humans, research on the mechanisms that mediate alcohol regulated preference in rats may shed light on the mechanisms that control human alcohol consumption.
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  • 144
    ISSN: 1432-2072
    Keywords: Key words Locomotion ; Activity ; Dose-response ; Time-course ; Anticholinergic drug ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: In order to facilitate direct comparisons of anticholinergic drug effects on activity, nine drugs were tested in one laboratory using a standardized procedure. Objective: The present study compared the effects of aprophen hydrochloride, atropine sulfate, azaprophen hydrochloride, benactyzine hydrochloride, biperiden hydrochloride, diazepam, procyclidine hydrochloride, scopolamine hydrobromide, and trihexyphenidyl hydrochloride on activity levels in rats. Methods: Both fine motor activity (reflecting smaller movements) and ambulatory activity (reflecting larger movements) were recorded for 23 h following drug administration in food-restricted rats. All drugs were administered during the light period of the photocycle. Results: Atropine, azaprophen, biperiden, scopolamine, and trihexyphenidyl increased both ambulations and fine motor activity significantly during the first hour post-injection, but the increased activity levels returned to vehicle control levels within 2–6 h post-injection. Benactyzine and procyclidine only increased fine motor activity significantly above vehicle control levels and activity levels returned to vehicle control levels within 2–3 h. Finally, aprophen and diazepam generally did not increase measures of activity significantly above vehicle controls at the dose ranges examined. Conclusions: Based on potencies relative to scopolamine, the potency of the drugs could be ranked as follows: scopolamine 〉 trihexyphenidyl 〉 biperiden 〉 azaprophen 〉 procyclidine 〉 benactyzine 〉 atropine 〉 aprophen. The comparison of drug effects on activity may be useful in selecting anticholinergic drug therapies with a minimal range of side effects. In addition, these data may reduce the number of anticholinergic drugs that need to be tested in comparison studies involving more complex behavioral tests.
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    Urological research 27 (1999), S. 174-179 
    ISSN: 1434-0879
    Keywords: Key words Apoptosis ; Ischemia-reperfusion ; Blood flow ; Ischemia ; Prostate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanisms involved in the castration-induced involution of the ventral prostate (VP) are not fully understood. It was recently reported that castration decreases blood flow in the VP in rats and that this occurs before the apoptotic involution of the organ. However, it is unknown whether a decrease in blood flow may trigger apoptosis in the VP, and this was therefore examined in this study. The right iliac artery was clamped for 1 h in adult male rats. After 24 h of reperfusion, the VPs were frozen or fixed. In situ end-labeling (ISEL) was used to identify apoptotic cells, and testosterone repressed prostatic message-2 (TRPM-2) was measured. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was used to identify proliferating cells. Clamping the right iliac artery reduced blood flow in the right VP to 0.17 of that in the contralateral lobe. This relative ischemia resulted in a threefold increase in the volume density of apoptotic epithelial cells on the treated side, but left cell proliferation unaffected. Testosterone substitution did not change this pattern. This study suggests that a transient period of relative ischemia may induce apoptosis in the rat ventral prostate. This may be of importance for the understanding of castration-induced prostatic involution.
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  • 146
    ISSN: 1434-0879
    Keywords: Key words Nonbacterial prostatitis ; Animal model ; Partial urethral obstruction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pathogenesis of nonbacterial prostatitis (NBP) is not understood mainly due to the lack of appropriate experimental models. We developed a new experimental model of NBP by inducing a partial obstruction of the urethra (PUO) in the rat. Male Wistar rats aged 12 weeks were used. PUO was produced by a nylon ligature on the urethra over a rubber tube. The tube was slipped out after the ligature had been tied. Two rats were examined histologically 6 h, 1 day, 3 days and 7 days after PUO. In another group, two rats were killed at 1, 3 and 7 days after the release of the PUO that had been left in place for 3 days. On day 3, another eight rats with PUO and eight control rats had 2 ml of urine in the bladder replaced by the same volume of lucifer yellow (LY; 10 μg/ml, MW 500), microperoxidase (MP; 20 μg/ml, MW 1900), horseradish peroxidase (HRP; 10 μg/ml, MW 40 000), or saline as control, respectively. Lymphocytic infiltration and interstitial edema were noted in the prostate following PUO, being most prominent on day 3. After the release of the PUO, these inflammatory changes gradually disappeared. Only LY was noted within the prostatic stroma of the rats 2 h after bladder instillation. Intraprostatic urinary reflux may be an etiologic factor in NBP. The present study showed that lower urinary tract obstruction caused NBP in the rat. Penetration of prostatic tissue by low-molecular-weight substances in the urine may trigger NBP.
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    Urological research 27 (1999), S. 41-47 
    ISSN: 1434-0879
    Keywords: Key words Ureter ; Histology ; Polyuria ; Diabetes mellitus ; Nephrectomy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of increased functional load on the macroscopical and histological appearance of the ureter was investigated. Sixty rats were divided into five groups: (1) sucrose-fed rats with non-osmotic polyuria; (2) diabetic rats with osmotic polyuria; (3) uninephrectomized rats; (4) sham-operated control rats; and (5) control rats. The 24-hour urinary volume was measured on days 7, 14 and 21. Growth of the kidney, ureter and bladder was investigated and the histological appearance of the ureter was further evaluated. Diabetic and sucrose-fed rats had comparable polyuria with a seven-fold increase in urinary output. The urinary volume for the remaining kidney was doubled in uninephrectomized rats. After 3 weeks, diabetic rats had increased weight of the kidney, ureter and bladder, sucrose-fed rats had increased weight of the bladder, whereas uninephrectomized rats had increased weight of the kidney and ureter. The cross-sectional area (CSA) of the ureter wall from control rats increased from the proximal to the distal portion. The size of the whole ureter from diabetic rats was dramatically increased, the CSA of the wall of the distal ureter portion being four times that of the controls. The CSA of the ureter wall from sucrose-fed rats was increased only in the distal portion, whereas the ureter from uninephrectomized rats was increased only in the proximal portion. The results demonstrate the importance of differentiating between different portions of the rat ureter when examining histological sections of this organ. Moreover, polyuria per se is shown to induce growth of the bladder and of the adjacent distal part of the ureter, whereas uninephrectomy and diabetes caused growth of the kidney and the upper parts of the ureter, in addition to the growth induced by polyuria.
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    Urological research 27 (1999), S. 476-482 
    ISSN: 1434-0879
    Keywords: Key words Urinary bladder ; Enterocystoplasty ; Cecocystoplasty ; Innervation ; Nerve growth ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Incorporation of bowel into the bladder (enterocystoplasty) has been widely used to increase bladder capacity. It has been reported by others that the response of smooth muscle from the cystoplastic segment of the intestine shifts from that of the intestine (relaxation to α-agonists and ATP) to that of the bladder (contraction to α-agonists and ATP). This suggests a functional integration of the intestinal muscle into the bladder; the mechanisms are unknown. The aims of the present study were (1) to elucidate if there are signs of bladder nerves sprouting across the anastomosis into the intestinal segment, and (2) to study what happens with the intrinsic innervation of the intestinal segment. As a model, we used cecocystoplasty in rats. The bladder was opened and a patch of cecum with intact vascular supply was anastomosed to the bladder. After two to 11 months the rats were sacrificed and the bladders mounted as wholemounts and stained for acetylcholinesterase-containing nerves, or embedded in paraffin for histology. A pronounced degeneration of the myenteric plexus was found in the cecal segments. In some areas, this had proceeded to the extent that the ganglia were isolated ovoid lumps of cells with no apparent connection to other ganglia. Areas lacking ganglia and nerve trunks but still with muscle could be found in all specimens. Abundant axon bundles were demonstrated sprouting from the cut bladder nerves close to the anastomosis. The bundles spread out in a fan-like pattern or were organized as fewer thicker nerves. There were many nerve bundles entering the cecal segment where they branched and the diameter decreased till they no longer became visible. Some nerves reached surviving lumps of myenteric ganglion cells. The results show that the bladder nerves sprout into the anastomosed cecal segment. It is reasonable to assume that these nerves are responsible for the changes in receptor pharmacological properties of the cecal smooth muscle towards that of bladder muscle.
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    European archives of oto-rhino-laryngology and head & neck 256 (1999), S. S38 
    ISSN: 1434-4726
    Keywords: Key words Taste buds ; Cytochalasin D ; Rhodamine-phalloidin ; Confocal laser microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of cytochalasin D on actin filaments in cells encircling taste pores were examined to clarify the functional role of actin filaments in the maintenance of taste pores in rat fungiform papillae, using a confocal laser microscope and a scanning electron microscope. Fluorescence in the taste pore cells was detected as a ring shape produced by actin staining with rhodamine-phalloidin. Treatment of fungiform papillae with cytochalasin D diminished the positive reactions in the taste pore cells and increased the inner diameter of the ring reactions. However, deformation of the taste pores in fungiform papillae was not detected under a scanning electron microscope after treatment with cytochalasin D. These findings suggest that the organization of actin filaments encircling the taste pores contributes to regulation of the taste pore’s size in rat fungiform papillae.
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    European archives of oto-rhino-laryngology and head & neck 256 (1999), S. 442-444 
    ISSN: 1434-4726
    Keywords: Key words Wheat germ agglutinin-conjugated ; horseradish peroxidase ; Neural regeneration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Regeneration of the mammalian central vestibular system was examined in rat. The lateral vestibulospinal tract (LVST) of infant rat was transected unilaterally at the level of C1–3. After a postoperative interval of several weeks, the LVST was examined by injecting an anterograde tracer (wheat germ agglutinin-conjugated horseradish peroxidase) into the lateral vestibular nucleus (LVN) and a retrograde tracer (Fast Blue) into the lumbar enlargement. More than half of the rats showed successful regeneration, indicating definite plasticity in the mammalian central vestibular system.
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  • 151
    ISSN: 1432-2277
    Keywords: Key words Xenotransplantation ; 15-deoxyspergualin ; Guinea pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study aimed to investigate the effects of 15-deoxyspergualin (DSG), tacrolimus (FK 506) and cyclosporin A (CyA), alone or in combination, on delayed xenograft rejection (DXR). We used the guinea-pig-to-C6-deficient (C6–)-PVG-rat heart transplantation model, since in this strain combination, hyperacute rejection is avoided. In C6- control rats, the guinea pig xenografts survived for 39.2 ± 6.3 h (mean ± SD). Splenectomy alone resulted in a xenograft survival of 71.8 ± 7.8 h, but the addition of CyA or FK 506 did not further improve graft survival (73.6 ± 3.0 h and 72.0 ± 17.6 h, respectively). In contrast, DSG treatment increased graft survival to a mean of 99.8 ± 9.2 h. When CyA or FK 506 was combined with DSG, no additional effects were observed (105 ± 24.3 h and 95.1 ± 5.6 h, respectively). DSG alone or in combination with FK 506 or CyA resulted in a significant reduction in the serum IgM levels and reduced the deposits of IgM and IgG in rejected grafts. However, all xenografts were still heavily infiltrated by ED1 + macrophages, regardless of the treatment used. Thus, DSG treatment resulted in moderate prolongation of xenograft survival in C6– rats. The effect seems to be related to suppression of xenoreactive antibody production. To prolong xenograft survival further, strategies that inhibit macrophage infiltration seem required.
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  • 152
    ISSN: 1432-5233
    Keywords: Key words Cadmium ; Diabetes ; VEP ; TBARS ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fifty-two healthy male Swiss albino rats, aged three months, were used in this study. They were divided into four groups: control (c), diabetic (D), cadmium (Cd), and diabetic + Cd (D+Cd). A diabetic condition was induced in D and D + Cd groups by administration of alloxane (5 mg/100 g). After this treatment, Cd and D + Cd groups were injected intraperitoneally with CdCl2 (2 mg/kg week). At the end of the 2-month experimental period, flash visual evoked potentials (FVEPs) of the four groups were recorded with disk electrodes attached with electrode paste 0.5 cm in front of and behind the bregma. The mean latencies off the P1, N1, P2, N2 and P3 components were significantly prolonged in the diabetic group compared with the control group. The mean latencies of P3 in the D + Cd group and of P1 and P3 in the Cd group were longer than those of the control group. P2N2 amplitude of Cd and D + Cd groups were significantly increased compared with the control group. On the other hand, thiobarbituric acid-reactive substances (TBARS) were determined as an indicator of lipid peroxidation. Our data showed that Cd treatment and diabetic condition caused a significant increase of lipid peroxidation in kidney, brain, retina and lens.
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  • 153
    ISSN: 1432-2072
    Keywords: Key words 7-OH-DPAT ; d-Amphetamine ; Dopamine ; Extinction ; Haloperidol ; Progressive-ratio ; Rat ; Self-stimulation ; Ventral tegmental area
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Progressive-ratio (PR) schedules, which have been widely used to study the reinforcing efficacy of various reinforcers (in particular IV psychostimulants), have been very seldom applied to the study of positively reinforcing electrical brain stimulation (EBS). In the present study, rats were required to emit a progressively increasing number of lever-presses (3,4,6,7,9,11,14,16, etc.) for access to successive reinforcers (periods of VTA self-stimulation). Each period of self-stimulation consisted of ten trains of square pulses of EBS; each train was available under a continuous reinforcement schedule. The number of periods of EBS earned during a session was deemed the breaking point (BP). After acquisition and stabilization of self-stimulation, a study was carried out to verify that changes in the strength of the EBS (i.e. changes in the frequency, the intensity or the pulse duration, one parameter at a time) induced changes in the BP. The effects of IP pretreatments with d-amphetamine, the dopamine D3/D2 receptor agonist 7-OH-DPAT and haloperidol were then assessed. Decreases in the strength of EBS decreased the BP. However, increasing the strength above training values resulted in minimal increases in the BP. d-Amphetamine (0.25–1 mg/kg) dose-dependently increased the BP; additionally, when the reinforcer was withheld (i.e. in conditions of extinction, with the stimulator turned off) d-amphetamine was also found to augment the BP. This might indicate that d-amphetamine preferentially potentiated the motivational (non-rewarded presses) aspects of VTA self-stimulation under this type of PR schedule. 7-OH-DPAT had biphasic effects: at low doses (0.01 and 0.03 mg/kg), it tended to decrease the BP while higher doses (1 and 3 mg/kg) robustly increased the BP. Under conditions of extinction, 7-OH-DPAT (1 mg/kg) had a tendency to increase the BP, but this effect was not statistically significant and did not approach the magnitude of effects observed with d-amphetamine. Haloperidol (0.08–0.48 mg/kg IP) dose-dependently reduced the BP, suggestive of a decrease in the reinforcing efficacy of the EBS. These results show that rats can be trained to self-administer EBS of the VTA under a PR schedule of reinforcement and that this behaviour is sensitive to disruption or potentiation of dopaminergic neurotransmission.
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  • 154
    ISSN: 1432-2072
    Keywords: Key words Neurosteroids ; GABAA receptor ; Sleep ; EEG spectral analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Progesterone has been shown to exert benzodiazepine-like effects on sleep, which suggests that they are mediated by an agonistic modulation of GABAA receptor functioning. To assess the involvement of GABAA receptors, we investigated the sleep responses to one dose of the GABAA antagonist picrotoxin (1.5 mg/kg) and progesterone (90 mg/kg), administered IP to eight rats alone and in combination, during the first 4 post-injection hours. Compared with vehicle, picrotoxin significantly delayed the latency to non-rapid eye movement sleep (non-REMS) and thereby decreased all sleep states, but barely affected the EEG activity within non-REMS. Progesterone significantly shortened non-REMS latency, increased pre-REMS, depressed low-frequency EEG activity (≤8 Hz) and augmented EEG activity in the higher frequencies within non-REMS. Except for the changes in high-frequency EEG activity, picrotoxin attenuated all effects of progesterone. These findings support the notion that GABAA receptors play an important role in the sleep effects of progesterone.
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  • 155
    ISSN: 1432-2072
    Keywords: Key words Ethanol ; Self-administration ; Dopamine ; Acetylcholine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study, the reactivity of striatal dopamine and dopamine-sensitive neurons in superfused striatal slices of ethanol-experienced rats was compared to that of ethanol-naive rats, 3 weeks after oral ethanol self-administration. During the acquisition phase (17 days), rats were offered increasing concentrations of ethanol (from 2 to 10%, 24 h per day) on an alternate-day schedule in a free choice with water. Following 2 weeks of unrestricted 10% ethanol consumption, the highest and lowest drinkers (representing about 25% of the upper and lower extremes of the total population) were selected. Preliminary experiments revealed that both groups of rats displayed a profound increase in ethanol consumption and preference 3 weeks after cessation of ethanol self-administration (deprivation effect). This deprivation effect was associated with an increase in electrically evoked release of [3H]dopamine from superfused nucleus accumbens slices, whereas the evoked [3H]dopamine release from caudate putamen slices remained unchanged. In slices of the caudate putamen, but not in nucleus accumbens slices, postsynaptic dopamine D1 receptor-stimulated cyclic AMP production was also enhanced. In addition, prior ethanol consumption enhanced the electrically evoked release of [14C]acetylcholine release in both striatal regions. Interestingly, the magnitude of these long-term neuroadaptations correlated with the amount of daily ethanol consumption, i.e. neuronal hyperresponsiveness in the striatum was more profound in the high than in the low ethanol drinkers. These data show for the first time that unrestricted free-choice ethanol consumption in rats is associated with a long-term increase in dopaminergic and cholinergic neurotransmission in the nucleus accumbens and caudate putamen. These (and other) neuroadaptations may underlie the enhanced motivation to self-administer ethanol and the maintenance of ethanol consumption long after deprivation.
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  • 156
    ISSN: 1432-2072
    Keywords: Key words Anhedonia ; Amphetamine ; Depression ; Progressive ratio ; Psychostimulant ; Rat ; Sucrose solution ; Withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Numerous studies have shown that withdrawal from sustained high doses of psychostimulant drugs such as cocaine or d-amphetamine produces depressive-like symptoms in both rats and humans. The majority of experiments with rodents have assessed the effects of amphetamine withdrawal on reinforcing electrical self-stimulation in different brain regions, but relatively few have examined effects on responding for natural reinforcers. In the present study, two groups of mildly food and water deprived male rats were trained to respond on a lever for a 4% sucrose solution under a progressive ratio schedule of reinforcement. One group was subsequently administered a 4-day regimen of injections of increasing doses of d-amphetamine based on a schedule shown previously to reduce self-stimulation behaviour. Break points were significantly reduced for up to 4 days after the termination of drug administration, suggesting a decreased motivation to obtain the natural reward. A further experiment demonstrated that the identical drug regimen produced no effect upon consumption of the 4% sucrose solution when it was freely available. These results demonstrate that the progressive ratio procedure may be a useful technique for evaluating changes in motivation for natural reinforcing stimuli following withdrawal from psychostimulant drugs.
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  • 157
    ISSN: 1432-2072
    Keywords: Key words MDMA (3 ; 4-methylenedioxymethamphetamine) ; Serotonin ; Psychopathology ; Human ; Rat ; Prepulse inhibition ; Habituation ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Prepulse inhibition of acoustic startle refers to the reduction in the startle response when the startling stimulus is preceded by a weak prepulse stimulus. This phenomenon provides an operational measure of sensorimotor gating that has been found to be reduced in patients with schizophrenia and rats treated with serotonin agonists or serotonin releasers. Objective: In this study, we compared the effects of a serotonin releaser, MDMA, on prepulse inhibition in laboratory rats and healthy human volunteers. In particular, we investigated whether MDMA disrupts PPI in humans as observed in animal studies. Methods: Rats were tested after placebo and MDMA in a counterbalanced order at an interval of 1 week, with separate groups of rats being used for each dose of MDMA (1.7, 5.4 and 17.0 mg/kg). On each test day, rats were first tested after no injections and retested 2 h later, 10 min after a subcutaneous injection of placebo or MDMA. For the human study, a placebo-controlled within-subject design and double-blind procedures were used. Subjects were examined twice at a 2 to 4 week interval after either placebo or drug administration (order being counterbalanced). On each test day, subjects underwent baseline testing including psychological and PPI measures. Ninety minutes later, subjects received placebo or MDMA (1.7 mg/kg PO) and were retested after 75 min during the peak of behavioral effects of MDMA. Results: As expected, MDMA decreased prepulse inhibition in a dose-related fashion in rats. In contrast, a typical recreational dose of MDMA (1.7 mg/kg, orally) increased prepulse inhibition in subjects experiencing robust psychological effects. Conclusions: This surprising disparity between the effects of the drug in rats and humans may reflect a species-specific difference in the mechanism of action of MDMA or in the behavioral expression of a similar pharmacological effect, or both.
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  • 158
    ISSN: 1432-2072
    Keywords: Key words Nicotinic receptor ; Dorsal hippocampus ; Anxiety ; Phobia ; Elevated plus-maze ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: The elevated plus-maze provides a test situation in which distinctive states of anxiety are elicited on trials 1 and 2 and the dorsal hippocampus has previously been shown to mediate the anxiogenic effects of (–)-nicotine in the social interaction test. Objective: To determine the effects of a wide dose range of (–)-nicotine on trial 1 and 2 in the plus-maze after systemic administration and whether the dorsal hippocampus is a site mediating the anxiogenic effect of nicotine. Methods: (–)-Nicotine (0.001, 0.005, 0.01, 0.05, 0.1, 0.5 and 1 mg/kg) was injected IP 30 min before testing for 5 min in the plus-maze. Rats receiving dorsal hippocampal infusions received bilateral infusions of 0.5 μl of artificial CSF or (–)-nicotine (0.1, 1, 4 or 8 μg). The needle was left in place for 50 s after injection and testing took place 3 min later. Rats tested on trial 1 were naive to the plus-maze, those tested on trial 2 had received a previous 5-min undrugged exposure to the maze 48 h earlier. Results: Low doses of (–)-nicotine (0.001, 0.005, 0.01, 0.05 and 0.1 mg/kg, IP) were without effect on either trial, but higher doses (0.5 and 1 mg/kg, IP) had anxiogenic effects on both trials, as shown by decreases in percentage time spent and percentage entries onto the open arms. Infusion of (–)-nicotine (0.1, 1, 4 and 8 μg) bilaterally into the dorsal hippocampus was without effect on trial 1, but 1 μg had an anxiolytic effect on trial 2, shown by an increased percentage time spent on the open arms. Conclusions: The results on both trials in the plus-maze after systemic administration of nicotine add to previous reports from the social interaction test that high doses of nicotine have anxiogenic effects. However, the effects of nicotine in the dorsal hippocampus are different in all three anxiety tests (anxiogenic in social interaction, ineffective on trial 1, anxiolytic on trial 2) showing that nicotinic cholinergic control in this brain region may vary depending on the state and/or type of anxiety generated by the test. The brain region(s) underlying the anxiogenic effects of IP nicotine on both trials in the plus-maze remain to be identified.
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  • 159
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Nornicotine ; Behavioral sensitization ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Nicotine, a tobacco alkaloid, is known to be important in the acquisition and maintenance of tobacco smoking. Nornicotine, an active nicotine metabolite, stimulates nicotinic receptors and may produce psychomotor effects similar to nicotine. Objective: The present study determined the effects of acute and repeated administration of nornicotine on locomotor activity and compared its effects with those of nicotine. Methods: R(+)-Nornicotine (0.3–10 mg/kg), S(–)-nornicotine (0.3–10 mg/kg), S(–)-nicotine (0.1–1 mg/kg) or saline was administered s.c. to rats acutely or repeatedly (eight injections at 48-h intervals). Activity was recorded for 50 min immediately after each injection. Results: S(–)-Nicotine produced transient hypoactivity, followed by dose-related hyperactivity. Repeated S(–)-nicotine administration resulted in tolerance to the hypoactivity and sensitization to the hyperactivity. Subsequent testing following a saline injection revealed evidence of conditioned hyperactivity. Acute administration of 0.3 mg/kg or 1 mg/kg R(+)- or S(–)-nornicotine produced no effect. Transient hypoactivity was observed at 3 mg/kg and 10 mg/kg R(+)-nornicotine and at 10 mg/kg S(–)-nornicotine. However, rebound hyperactivity was not observed following acute administration of either nornicotine enantiomer, suggesting that nornicotine-induced psychomotor effects differ qualitatively from those of S(–)-nicotine. Repeated R(+)-nornicotine resulted in tolerance to the transient hypoactivity, however hyperactivity was not observed. Repeated S(–)-nornicotine resulted in tolerance to the hypoactivity and the appearance of hyperactivity. Repeated administration of either nornicotine enantiomer resulted in a dose-dependent alteration in response to a 1 mg/kg S(–)-nicotine challenge, suggesting some commonalities in the mechanism of action. Conclusion: Nornicotine likely contributes to the neuropharmacological effects of nicotine and tobacco use.
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  • 160
    ISSN: 1432-2072
    Keywords: Key words Hippocampus ; Lesion ; Glutamate receptor and release ; Dopamine receptor ; Locomotor activity ; Schizophrenia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 6-week and 8-week-old rats (pre- and postpubertally) with neonatal excitotoxic lesions of the ventral hippocampus with ibotenic acid (IBO), we have studied apomorphine-induced motor activity and glutamate and dopamine D1 and D2 binding sites in the hippocampus, striatum, nc. accumbens and frontal cortex as well as K+-stimulated (3H)-D-aspartate release from hippocampal and frontal cortical slices. Specific glutamate binding was enhanced in the frontal cortex of 8-week-old IBO-treated animals, whereas that in other brain regions remained unchanged. Both D1 and D2 binding sites were downregulated in the striatum without changes in other brain structures. In 6-week-old rats, neither the glutamate nor the dopamine binding sites were altered. The amino acid release from hippocampal and frontal cortical slices of adult IBO treated rats was significantly decreased in comparison to controls, whereas in 6-week-old rats, no significant alterations were detectable. The additionally monitored motor activity was enhanced only in adult IBO-lesioned rats after apomorphine pretreatment. The present data are in agreement with the hypothesis of hyperactive dopamine and hypoactive glutamate systems in schizophrenia and are discussed in the light of schizophrenia-like behavioral changes in rats after postnatal hippocampal IBO lesion.
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  • 161
    ISSN: 1432-2072
    Keywords: Key words Cocaethylene ; Cocaine ; Alcohol ; Interaction ; Schedule-controlled responding ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Cocaethylene is a unique metabolite of cocaine, produced only in the presence of alcohol. This metabolite is pharmacologically, physiologically and behaviorally active. Further, it has been reported to interact pharmacokinetically with both cocaine and alcohol, an interaction that may mediate, in part, the interaction of cocaine and alcohol. Although cocaethylene has been shown to interact with both cocaine and alcohol, behavioral assessments of these interactions are limited. Objectives: To examine directly the behavioral interactions between cocaethylene and cocaine and between cocaethylene and alcohol, the present study assessed the effects produced by these combinations on schedule-controlled responding. Methods: Rats were first administered cumulative doses of cocaethylene, cocaine and alcohol to assess their effects alone on responding. Following this, doses of cocaethylene were combined with cumulative doses of cocaine or alcohol. Additionally, doses of cocaine or alcohol were given in combination with cumulative doses of cocaethylene. Results: When administered alone, cocaethylene, cocaine and alcohol produced dose-related decreases in responding. Further, cocaethylene shifted the dose–response functions for both cocaine and alcohol to the left and down, while cocaine and alcohol shifted the dose–response function for cocaethylene to the left and down. An isobolographic analysis revealed that these interactions were additive in nature. Conclusions: The present study suggests behavioral interactions between cocaethylene and cocaine and between cocaethylene and alcohol. The contribution of cocaethylene to the enhanced effects produced by the co-administration of cocaine and alcohol was discussed.
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  • 162
    ISSN: 1435-2451
    Keywords: Key words Liver transplantation ; Bile salt ; Tauroursodeoxycholate ; Rat ; Reperfusion injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Introduction: Tauroursodeoxycholate (TUDC) is used routinely in the treatment of cholestatic liver disease. The present study was designed to determine whether it would mitigate ischemia/reperfusion injury in an in vivo pig liver-transplantation model. Methods: Transplantation was performed in 12 animals after a preservation time of 8 h. In the control group (n=6), 0.9% saline was infused into the donor. In the experimental group (n=6), TUDC was given intravenously at a rate of 2 µmol/kg body weight per minute. In the recipient, infusion was started at the time of reperfusion; saline was infused for 400 min in the control group, TUDC for the same duration at a rate of 0.2 µmol/kg body weight per minute in the experimental group. Blood was drawn for determination of liver enzymes. Bile samples were collected and bile flow (BF) and bile salt secretion rate (BSSR) were determined. Results: One-week survival was 92% and not different among groups. Liver enzymes were lower in the TUDC group than the saline group. Prior to TUDC infusion in the donor animals, there were no differences in BF and BSSR. After infusion of TUDC, BF and BSSR were highly significantly different than the control group. Discussion: Infusion of TUDC in pig livers protects against ischemia/reperfusion injury in vivo. This might be due to the membrane-stabilizing effect of TUDC. Preconditioning of liver grafts with TUDC could potentially lead to improved liver function post-transplantation.
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  • 163
    ISSN: 1432-0533
    Keywords: Key words Clomethiazole ; Rat ; Spinal cord-injury ; Neuroprotection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clomethiazole (CMZ) has a neuroprotective effect in experimental focal and global forebrain ischemia. This neuroprotective effect may depend on its ability to enhance GABA receptor activity. We have studied the effect of pretreatment with CMZ on motor function recovery and nerve cell damage after spinal cord injury (SCI). Rats were randomized and 30 min before SCI they received a single intraperitoneal dose of CMZ (150 mg/kg) or saline. The spinal cord was injured with a 50 g (4.5 g/mm2) load, applied over the exposed dura, through a curved rectangular plate (2.2 × 5.0 mm) for 5 min at T8–9. The animals became paraplegic 1 day after injury. The rats were evaluated for recovery of hind limb motor function. All animals recovered to some extent over the observation period of 12 weeks. However, hind limb motor function was significantly better in the animals pretreated with CMZ. At 12 weeks the rats were killed and perfused/fixed for morphological investigations. Microtubule-associated protein 2 (MAP2) immunostaining was used to stain neurons and dendrites and Luxol-fast blue to stain myelinated tracts of the white matter. The injured segment of the spinal cord showed severe atrophy, distortion, cavitation and necrosis of grey and white matter. Compared to uninjured controls the transverse sectional area was reduced to 32.7 ± 4% in untreated animals but only to 38.5% ± 4.1 in CMZ-treated animals. MAP2 staining showed that, compared to uninjured controls, grey matter was reduced to 7.4 ± 2.7% in saline-treated injured animals and to 22.7 ± 5.4% in CMZ-treated rats. Our results thus show that in this model CMZ improves hind limb motor function and attenuates the morphological damage to the spinal cord.
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  • 164
    ISSN: 1573-0603
    Keywords: Dichloromethylene diphosphate ; Hepatic stellate cell isolation ; Liposome ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Hepatic perisinusoidal cell population consists of hepatic stellate cells, Kupffer cells, endothelial cells, and Pit cells. These cells are isolated by enzymic digestion and purified by density gradient centrifugation. With isolation of stellate cells, conventional method is unable to eliminate the contamination of Kupffer cells because the densities of these two cells are similar. We report here an improved method for isolation of highly purified hepatic stellate cells, using dichloromethylene diphosphate (CL2MDP), which has selective cytotoxicity of Kupffer cells. Three days after the single intravenous administration of liposome-encapsulated CL2MDP, the Kupffer cells disappeared almost completely from the liver. Following Percoll density gradient centrifugation, the purity of the hepatic stellate cells exceeded 98% without any contamination of the Kupffer cells. Kupffer cells are reported to affect the physiological functions of stellate cells. The availability of highly purified stellate cells will facilitate the investigation of their functions in primary culture.
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  • 165
    ISSN: 1432-0878
    Keywords: Key words Neurofilament ; Basket cell ; Pinceau ; Golgi apparatus ; Calcium binding protein ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract NCS-1 (neuronal calcium sensor) is a recently characterized member of a highly conserved neuron-specific family of calcium-binding proteins, which also includes frequenin and recoverin. The cellular and subcellular distributions of NCS-1 in the rat nervous system were investigated using light- and electron-microscopic immunohistochemistry. NCS-1 immunoreactivity was localized to neuronal cell bodies and axons throughout the brain and spinal cord but not to glial cells. The most intense labeling was observed in myelinated axons, the axonal ramifications of the basket cell in the cerebellar cortex, and large neurons in the brainstem and pons. These same structures were also characterized by heavy labeling for neurofilament protein, as determined by double-labeling experiments. Most axon terminals were unlabeled or only lightly labeled. The most remarkable subcellular staining occurred in the perikarya where intense labeling was associated with the membranes of the trans saccules of the Golgi apparatus. The widespread distribution of NCS-1 indicates that it may be active in a variety of calcium-dependent neuronal functions, whereas the specific subcellular localization to the Golgi apparatus and neurofilament-rich structures suggests a specialized role in calcium regulated protein trafficking and cytoskeletal interactions.
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  • 166
    ISSN: 1432-0878
    Keywords: Key words Glial cell line-derived neurotrophic factor ; GDNF ; Ret ; GDNFR-α ; Brain-derived neurotrophic factor ; BDNF ; NT-3 ; NT-4 ; trk receptors ; Thyroid tissue ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Levels of mRNA for neurotrophins (brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT-3; neurotrophin 4, NT-4) and their receptors (trkA, trkB, trkC) and for glial cell line-derived neurotrophic factor (GDNF) and its receptors (ret, GDNFR-α) were measured in rat thyroid tissue by ribonuclease protection assays. In thyroid tissue the NT-3 mRNA level was threefold lower and the NT-4 mRNA level sixfold higher than those detected in adult rat hippocampus, while BDNF mRNA was undetectable. Very low levels of mRNA for truncated trkB and trkC receptors and no catalytic trkA, trkB or trkC were found. In conclusion NT-3 and NT-4, but not the corresponding functional receptors, are expressed in the thyroid tissue. Therefore, it is unlikely that these factors serve a direct local autocrine or paracrine function in thyroid cell types, and a target-derived mode of action on neurons innervating the thyroid tissue is suggested. An opposite result has been found for the neurotrophic factor GDNF: thyroid tissue showed a high level of transcripts for the GDNF receptor subunits (GDNFR-α and Ret), while GDNF mRNA was undetectable. The in situ hybridization analysis of GDNFR-α and ret mRNA revealed an interesting difference in the cell distribution of these transcripts: ret mRNA is selectively expressed in a subpopulation of cells scattered in the follicular epithelium and in the interfollicular spaces, while GDNFR-α expression is more homogeneous and widespread, including the more abundant cell type of the thyroid gland: the follicular cell. Double-labeling in situ hybridization/immunocytochemistry experiments, with a specific marker (calcitonin), showed that parafollicular cells express ret but not GDNFR-α. This differential distribution of the GDNF receptor components (GDNFR-α and ret) may reflect a peculiar biological role in intercellular communication in the thyroid gland.
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  • 167
    ISSN: 1432-0878
    Keywords: Key words Water channel protein ; Aquaporin ; AQP5 ; Rat ; Salivary glands ; Immunolocalization ; Secretory stimulation ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Aquaporin-5 (AQP5) is a water channel protein and is considered to play an important role in water movement across the plasma membrane. We raised anti-AQP5 antibody and examined the localization of AQP5 protein in rat salivary and lacrimal glands by immunofluorescence microscopy. AQP5 was found in secretory acinar cells of submandibular, parotid, and sublingual glands, where it was restricted to apical membranes including intercellular secretory canaliculi. In the submandibular gland, abundant AQP5 was also found additionally at the apical membrane of intercalated duct cells. Upon stimulation by isoproterenol, apical staining for AQP5 in parotid acinar cells tended to appear as clusters of dots. These results suggest that AQP5 is one of the candidate molecules responsible for the water movement in the salivary glands.
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  • 168
    ISSN: 1439-6327
    Keywords: Key words Bone ; Deoxypyridinoline ; Osteocalcin ; Rat ; Treadmill running
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was designed to provide data on the effects on femoral bone of endurance training starting only 3 months after orchidectomy in rats. A total of 70 Wistar male rats were used at 8 weeks of age. On day 0 of the experiment, 10 rats were killed by cervical dislocation to be used as first controls. Among the 60 other animals, half was surgically castrated (CX) or sham operated (SH). On day 90, 10 CX and 10 SH were killed and used as intermediary controls (ICX and ISH). Among the other 20 CX and 20 SH, 10 within each group (CXE, SHE) were selected for treadmill running (60% maximal oxygen uptake, 1 h · day−1, 5 days · week−1 for 12 weeks). The 20 other rats were used as sedentary controls (CXR, SHR) and killed (as runners) on day 180. On day 90 femoral bone density (BMD) and mineral content (BMC) were lower in ICX than in ISH. On day 180 total femoral BMD was lower in CXR than in CXE. Simultaneously metaphyseal femoral BMD was lower in CXR than in CXE, SHR or SHE. Furthermore, at that time, no significant difference concerning BMD and BMC was observed between SHR and CXE. This would indicate that treadmill running starting only 3 months after orchidectomy is able to restore BMD and BMC to control values, mainly by inhibiting bone resorption (as shown by decreased urinary deoxypyridinoline excretion in CXE) without decreasing osteoblastic activity (evaluated by plasma osteocalcin concentration).
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    European journal of applied physiology 80 (1999), S. 344-352 
    ISSN: 1439-6327
    Keywords: Key words Endurance running ; Bone density ; Deoxypyridinoline ; Osteocalcin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This experiment was performed to study the effects on femoral bone of endurance training performed during the 3 months before orchidectomy in rats which were then killed 90 days later. A total of 70 male Wistar rats were used at 8 weeks old. One day 0 of the experiment, 10 rats were killed by cervical dislocation and used as first controls. Among the 60 others, 30 were selected for treadmill running (60% maximal oxygen uptake, 1 h · day−1, 6 days · week−1 for 90 days). The 30 other rats remained at rest. On day 90, 10 exercised (IE) and resting (IR) rats were killed and used as intermediary controls. Among the 20 other animals of each group, 10 were surgically castrated (CXE, CXR) or 10 sham-operated (SHE, SHR) and killed on day 180. On day 90 femoral failure load (three-point bending test) was greater in IE than in IR. Simultaneously, the deoxypyridinolinuria was lower in IE than in IR. On day 180, femoral bones were thinner in CXR than in CXE. The lowest values for trabecular bone are in the distal femoral metaphysis were measured in CXE and CXR rats, but the value measured in CXE was no different from that measured in SHR. Simultaneously total femoral bone density was lower in CXR than in SHE, while no difference concerning femoral metaphyseal density was observed between CXE and SHR. These results confirmed that endurance running increased femoral bone growth and modelling and femoral trabecular area, and thereby peak bone mass, in 8-month-old male rats. In resting animals, castrated after the training period, androgen deficiency decreased femoral density, mineral content and trabecular area. This decrease was not observed in castrated but previously exercised rats. Thus, by increasing peak bone mass, it was considered that endurance training may have a preventive effect against orchidectomy-induced bone loss.
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  • 170
    ISSN: 1573-9104
    Keywords: Bioavailability ; Magnesium ; Hijiki ; Sodium alginate ; Rat ; Wakame
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The bioavailability of magnesium from Wakame and Hijiki, and the effects of alginic acid on absorption of dietary magnesium were examined in five groups of rats fed either control, Wakame, Hijiki, AW (containing the same amount of alginate as in the Wakame) and AH (containing the same amount of alginate as in the Hijiki) diets, and animals fed a low magnesium diet (LMg) (twentieth amount of magnesium in the original mineral mixtures as the control). Food intake and body weight gain were decreased by adding sodium alginate to the diets. A large amount of calcium accumulated only in the kidneys of the rats fed the LMg diet. Serum magnesium concentration decreased only in the LMg group. The magnesium content in the defatted left femurs did not differ between the control and Wakame fed animals and also among the animals eating Wakame, Hijiki and AW diets. The breaking force of the right femurs did not differ among all the groups except the LMg group. The ratio of apparent magnesium absorption (%) of the control, LMg, Wakame, Hijiki, AW and AH groups was 82.2, 72.7, 66.9, 50.8, 69.3 and 54.2 in the first experimental period, and was 75.3, 52.1, 57.7, 46.9, 62.6 and 60.5 in the second experimental period, respectively. It was clear that the bioavailability of magnesium in the Wakame fed rats was higher than in those eating the Hijiki. Large amounts of sodium alginate lowered magnesium absorption from the diet.
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  • 171
    ISSN: 1432-0878
    Keywords: Key words Axonal transport ; Purkinje cell ; Organotypic culture ; Microinjection ; Antimitotic drugs ; Cytoskeleton ; Dendritic transport ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Axonal and dendritic transport in single Purkinje neurons of cerebellar slice cultures was quantified as single transport distances. Examination of the cells within a vital tissue was regarded as being an approach to the in situ condition. The Purkinje cells were organotypically integrated in the in vitro tissues and extended long axonal projections connecting synapses to the target neurons. The tracer horseradish peroxidase (HRP) was applied via microinjection to the somata of the Purkinje cells and the injected neurons were incubated thereafter for defined time-intervals. The tracer was transported anterogradely into the neuron processes. The measurements on both the axonal and the dendritic transport of microinjected HRP revealed continuous transportation with increasing times of postincubation. This transport was reduced by the use of microtubule-depolymerizing drugs. The axonal transport of the tracer was either retarded in colchicine-treated cells or continuously reduced for up to 50% in vinblastine-treated neurons. Thus, a correlation of axonal transport to the microtubules was demonstrated. The dendrites were filled with the tracer after 60 min of postincubation. Dendritic transport was reduced by the use of vinblastine, and not significantly by colchicine. The results strongly support the dependence of neuronal transport on microtubules as a component of the cytoskeleton.
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  • 172
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    Age 22 (1999), S. 19-25 
    ISSN: 1574-4647
    Keywords: Norepinephrine ; Aging ; Free Radicals ; Antioxidants ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present review provides an overview of age-related changes in cerebellar β-adrenergic function, associated motor learning, causal agents and possible treatments. Norepinephrine acts as a neuromodulator of Purkinje cell activity. With aging, however, the ability of norepinephrine to modulate Purkinje cell activity and specifically GABAergic inhibition of Purkinje cell activity is decreased. This age-associated deficit in cerebellar noradrenergic function correlates with deficits in acquisition of a motor learning task. Aged rats are delayed in acquiring a motor learning task that requires rats to adjust footfalls in order to cross a runway. The degree of deficit in cerebellar β-adrenergic activity correlated positively with the degree of impairment in task acquisition. One possible causal agent for the β-adrenergic deficit is free radical damage. Hyperoxia, which may generate free radical damage, induces cerebellar β-adrenergic deficits in young rats but diet restriction and treatment with antioxidants can delay or reverse age-related deficits in cerebellar β-adrenergic function in old rats.
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  • 173
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    Cell & tissue research 296 (1999), S. 235-246 
    ISSN: 1432-0878
    Keywords: Key words Transplantation ; Parkinson’s disease ; CNS fetal development ; CNS differentiation ; Neurotrophic factors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have previously shown that a combination of the cytokines interleukin (IL)-1, IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF) can convert rat fetal (E14.5) mesencephalic progenitor cells into tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in vitro. The experiments described here characterize the mesencephalic progenitor cells and their cytokine-induced conversion into dopamine (DA) neurons. For all experiments, we used bromodeoxyuridine (BrdU)-ir cultures of (E14.5) mesencephalic progenitor cells that had been expanded at least 21 days. We first demonstrated that IL-1 induced DA neuron conversion in mesencephalic progenitors, but not in striatal progenitors (P〈0.001). Thus, these cells should be classified as lineage-restricted progenitors, and not omnipotent stem cells. To further characterize cell populations in these cultures, we used monoclonal antibodies against Hu (an early marker for neurons), growth-associated protein (GAP)-43 (a marker for neuronal process extension), TH (a marker for DA neurons), and glial fibrillary acidic protein (GFAP, a marker for astrocytes). We assessed (E14.5) mesencephalic progenitor cell cultures (plated at 125,000 cells/cm2) incubated in the cytokine mixture (described above) or in complete media (CM, negative control). Following 7 days incubation, GFAP-positive cells formed a nearly confluent carpet in both types of cultures. However, numbers of Hu-ir and GAP-43-ir cells in the cytokine-incubated cultures far exceeded those in CM-incubated controls (P=0.0003, P=0.0001, respectively), while numbers of TH-ir cells were 58-fold greater in the cytokine-incubated cultures versus CM-incubated controls. The TH phenotype persisted for 7 days following withdrawal of the differentiation media. Numerous double-labeled cells that were BrdU-ir and also TH-ir, or Hu-ir and also TH-ir, were observed in the cytokine-incubated cultures. These data suggest that cytokines ”drive” the conversion of progenitor cells into DA neurons.
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  • 174
    ISSN: 1432-0878
    Keywords: Key words Subcommissural organ ; Isograft ; Xenograft ; Reissner’s fiber ; Cerebrospinal fluid ; Rat ; Bovine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The subcommissural organ (SCO) secretes glycoproteins into the cerebrospinal fluid (CSF) that aggregate and form Reissner’s fiber (RF). The factors involved in this aggregation are not known. One factor may be the hydrodynamics of the CSF when flowing through the aqueduct. This hypothesis was tested by isografting rat SCO and xenografting bovine SCO into the lateral ventricle of rats. Xenografts were either fresh bovine SCO or explants cultured for 30 days before transplantation. The grafts were investigated by electron microscopy and immunocytochemistry using antibodies against RF glycoproteins, serotonin and the glucose transporter I. Maximal time of transplantation was 43 days for isografts and 14 days for xenografts. The isografts were not reinnervated but were revascularized; they secreted into the ventricle RF glycoproteins that became progressively packed into pre-RF and RF structures identical to those formed by the SCO in situ. RF was confined to the host ventricle and at its distal end the constituent proteins disassembled. Xenografts were neither reinnervated nor revascularized and secreted into the host ventricle a material that never formed an RF. These findings indicate that the CSF factor responsible for the formation of RF is species specific, and that this process does not depend on the hydrodynamics of the CSF. The blood vessels revascularizing the isografted SCO acquired the characteristics of the vessels irrigating the SCO in situ, namely, a tight endothelium displaying glucose transporter I, and a perivascular space containing long-spacing collagen, thus indicating that basal release of glycoproteins may also occur in the grafted SCO.
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  • 175
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    Biologie in unserer Zeit 29 (1999), S. 12-17 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Die heutigen Wälder, die man in Europa vorfindet, waren nicht immer dort. VOr 22000 Jahren - im Hochglazial - gab es nur im Mittelmeergebiet die klimatischen Voraussetzungen für das Wachstum von Bäumen. Allerdings waren dies meist keine dichten Wälder, sondern Steppen mit einzelnen Baumgruppen. Das bedeutet jedoch, daß die heute in Europa wachasenden Bäume während der letzten 12000 Jahre - also seit dem Ende der letzten Eiszeit - nach Mittel- und Nordeuropa eingewandert sein müssen. Am Beispiel der Waldbäume Eiche (Quercus), Hainbuche (Carpinus), Fichtet (Picea) und Tanne (Abies) soll diese Einwanderung aufgezeigt werden.
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    Biologie in unserer Zeit 29 (1999), S. 6-11 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Irgendwie wird niemand mehr richtig glücklich mit der Wissenschaft, so erfolgreich sie auch ist und so sehr unsere alltäglichen Verrichtungen von ihren Ergebnissen und Lieferungen auch abhängen. Das Verständnis der öffentlichen Beobachter nimmt trotz aller Bemühungen nicht zu, sondern ab, und die professionellen Betreiber sehen sich unentwegt nach ihrer Verantwortung gefragt und in ethische Debatten verstrickt. Die ursprüngliche Idee, daß Wissenschaft nur gut sein kann, hat massiv an Überzseugungskraft verloren, und dieser Verlust tritt deshalb besonders deutlich hervor, weil man spürt, wie die alte Basis der Rationalität brüchig geworden ist, ohne einen neuen Grund zu erkennen, auf den man in Zukunft bauen kann. Dabei übersehen wir ein Fundament, auf dem Menschen immer schon gestanden haben und zu dem sie also auch zu jeder Zeit wieder zurückkommen können.
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    Biologie in unserer Zeit 29 (1999), S. 55-55 
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    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
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  • 178
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    Biologie in unserer Zeit 29 (1999), S. 56-57 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
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    Biologie in unserer Zeit 29 (1999), S. 60-60 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
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    Biologie in unserer Zeit 29 (1999) 
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    Topics: Biology
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  • 181
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    Biologie in unserer Zeit 29 (1999), S. 90-97 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Die fossile Überlieferung aus den letzten präkambrischen Jahrmillionen deutet darauf hin, daß gelatinös organisierte Formenj, also quallenähnlich gebaute Organismen, die das marine Pelagial (den freien Wasserkörper des Meeres) besiedelten ‘3’. Was sie dort vorfanden war jedoch wenig labensfreundlich. Zwar wimmelte das Meer von bakterien und Protozoen, aber im wesentlichen waren die riesigen Wasserräume leer und unbesiedelt. Crustaceen und andere Organisationsformen waren - wenn die Befunde stimmen - noch in der Entwicklungsphase beziehungsweise noch nicht zu der pelagischen Lebensweise übergegangen. Wie überlebten die quallenförmigen Organismen in dieser Umwelt, und warum leben sie noch heute in allen Bereichen des Meeres, von der Flach- bis in die Tiefsee, von den Polen bis zu den Tropen? Der pelagische Lebensraum beinhaltet Tausende von Arten, die viel “höher” organisierten Gruppen angehören, die schneller und kräftiger sind. Wieso wurden die gelatinösen Plankter nicht in irgendeine skurrile Nische gedrängt oder über die Konkurrenz völlig ausgeschaltet? Mögliche Antworten auf diese Fragen finden wir in der Gegenwart.
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    Biologie in unserer Zeit 29 (1999), S. 117-117 
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    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
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  • 183
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    Biologie in unserer Zeit 29 (1999), S. 110-116 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Als Fertilitätsrate bezeichnet man die Zahl der Geburten pro Frau in ihrer Lebensspanne. Wenn Zu- Oder Abwanderung in einer Population gering sind, läßt eine Fertilitätsrate von 2,0 eine konstante Bevölkerungszahl erwarten. Bei der Entwicklung der Erdbevölkerung beobachtet man in den industrialisierten Ländern derzeit keinen Anstieg. Die Fertilitätsrate liegt in den USA bei 2,1 und in Europa durchschnittlich bei 1,4. Mit 1,2 und 1,15 haben Italien und Spanien dabei die weltweit niedrigsten Fertilitätsraten. Somit ist örtlich sogar ein Bevölkerungsrücksgang zu erwarten. Auch in ostasiatischen Ländern wie China und Korea hat sich der Bevölkerungszuwachs verlangsamt. In Südasien und in afrikanischen Ländern wie China und Korea hat sich der Bevölkerungszuwachs verlangsamt. In Südlich der Sahara finden wir jedoch nach wie vor relativ hohe Gebeurtenraten. Im westafrikanischen Nigeria liegt die Fertilitätsrate bei 6,3. Für Indien und Pakistan werden Werte von 3,5 und 5,6 angegeben. Es gibt also noch viele Regionen mit einer hohen Fertilitätsrate. Manche Wissenschaftler gehen sogar davon aus, daß sich die Zahl entsprechender Staaten eher noch erhöhen wird ‘7’. Deshalb weichen auch die Schätzungen voneinander ab, bei welcher Bevölkerungszahl Wachstumsstillstand eintreten wird. Viele Demographen gehen davon aus, daß sich die Erdbevölkerung bis zum Jahr 2050 bei 10 Milliarden stabilisieren wird ‘9’. Andere schätzen, daß danach ein weiterer Ansteig auf etwa 12 Milliarden menschen zu erwarten ist ‘7’. Der Rückgang der Geburtenzahlen in den industrialisierten Ländern wurde mit kontrazeptiven Maßnahmen erzielt, die uns schon lange zur Verfügung stehen und die gut eingeführt sind. Auf den ersten Blick Sch eint es somit aus bevölkerungspolitischer Sicht auf dem Gebiet der Kontrazeption keinen zwingenden Bedarf für Neuentwicklungen zu geben. Dennoch sind Forschungsaktivitäten im Gang, die auf eine pharmakologische Kontrazeption beim Mann gerichtet sind. Im vorliegenden Artikel werden neben den traditionellen Möglichkeiten, die dem Mann zur Kontrazeption offenstehen, der wissenschaftliche Hintergrund und der Entwicklungsstand einer “Pille für den Mann” vorgestellt.
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    Biologie in unserer Zeit 29 (1999), S. X 
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    Biologie in unserer Zeit 29 (1999), S. 151-157 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Generell ist der Markt für gentechnisch veränderte Pflanzen und daraus hergestellte Produkte in den letzten Jahren gewachsen. In Deutschland zeigen sich indessen eher verhaltene Auswirkungen dieser Entwicklung ‘3’. Die wirtschaftliche Entfaltung der Gentechnik und Biotechnologie ist in Deutschland noch gering. Als ein Maß für den Entwicklungsstand der Gentechnik in der Pflanzenzüchtung ‘2’ und damit unter anderem auch deren Auswirkung auf die Futter- und Lebensmittelproduktion kann die Anzahl von Freisetzungsvorhaben mit gentechnisch veränderten Organismen (GVO) gelten. Von den rund 1300 Freisetzungsvorhaben im Bereich der EU entfallen 90 auf Deutschland. Im Vergleich zu den anderen EU-Mitgliedsstaaten rangiert Deutschland damit auf dem siebenten Platz.
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    Biologie in unserer Zeit 29 (1999), S. 188-188 
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    Keywords: Life and Medical Sciences
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  • 187
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    Biologie in unserer Zeit 29 (1999), S. 177-183 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Vielfalt in allen Erscheinungsformen kennzeichnet schon die unbelebte und in noch stärkerem Maße die belebte Natur. Dagegen drängt die Nutzung von Naturkräften durch den Menschen, insbesondere in ihren weiter entwickelten und technisierten Formen stets auf Vereinfachung. So werden landwirtschaftliche Kulturpflanzen bei ein- bis mehrjähriger Nutzung im Regelfall in Reinkultur angebaut, ganz im Gegensatz zur standorttypischen Artenvielfalt eines natürlichen Pflanzenbestandes. Lediglich die verbliebene Unkrautflora erinnert dann and die ursprüngliche Artenvielfalt einer Pflanzengesellschaft. Es kommt hinzu, daß sich landwirtschaftlicher Pflanzenbau auf nur wenige anbauwürdige Kulturpflanzenarten konzentriert. Weltweit nimmt das Ackerland etwa 10 % der Landoberfläche der Erde ein, die mit nur etwa 30 Kulturpflanzenarten von überregionaler Bedeutung bestellt werden. Allein 37,4% davon sind dem Anbau von nur dreif für die Ernährung der Menschheit besonders bedeutsamen Arten (Weizen, Resi und Mais) gewidmet. In Deutschland werden gegenwärtig sogar 33% der Landoberfläche als Ackerland genutzt. Von den insgesamt etwa 14 bei uns häufiger anzutreffenden Kulturpflanzenarten besetzen die drei dominierenden Arten (Winterweizen, Mais und Wintergerste) dabei 48% der Anbaufläche. Landwirtschaftlicher Pflanzenbau wird also generell artenarm betrieben.Die zweite Ebene bilogischer Vielfalt im landwirtschaftlichen Pflanzenbau stützt sich auf die mehr oder weniger regelmäßige Folge verschiedener in Reinkultur angebauter Kulturpflanzenarten. Bozogen auf die Gesamtfläche eines Betriebes order die Feldflur einer Gemeinde ergibt sich dann noch immer ein abwechslungsreiches Gesamtbild verschiedener Aussaat-, Blühund Erntezeiten. Für artenreiche Fruchtfolgen lassen sich darüber hinaus viele, für die Bodenbewirtschaftung vorteilhafte Argumente anführen. Die hohe Schlagkraft der vollmechanisierten Betriebe und die beliebige Verfügbarkeit von Dünge- und Pflanzenschutzmitteln in Verbindung mit artunterschiedlichen Ertrags- und Preisrelationen haben jedoch auf intensive bewirtschafteten Betrieben in günstigen Lagen zu einer oft drastischen Reduktion der Pflanzenproduktion (auf den Anbau von nur noch drei, manchmal sogar nur zwei Arten) geführt, von denen der jeweils höchste Beitrag zur Deckung der Betriebskosten erwartet werden kann.Inzwischen hat sich jedoch die Erkenntnis durchgesetzt, daß die Aufrechterhaltung “biologischer Diversität” ein wesentliches Element zur Sicherung der “Nachhaltigkeit” der landwirtschaftlichen Pflanzenproduktion darstellt. Dies hat in der Konferenz von Rio (1992) im Rahmen der Agenda 21 zum Abschluß einer “Konvention über Biologische Vielfatl” geführt, der auch die Bundesrepublik Deutschland beigetreten ist.Mit dem Begriff biologische Vielfalt werden in dieser Konvention nicht nur Naturschutzverpflichtungen zur Sicherung des Erhalts bedrohter Tier- und Pflanzenarten übernommen, sondern es geht zu einem wesentlichen Teil auch um die 3. Ebene der biologischen Vielfalt in Form der genetischen Vielfalt innerhalb der für die Welternährung grundlegend bedeutsamen Kulturpflanzenarten. In diesem Zusammenhang soll hier gefragt werden, ob mit der Einführung transgener Nutzpflanzen neben ihrem wirtschaftlichem Nutzen auch Risiken für die biologische Vielfatl verbuden sind.
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    Biologie in unserer Zeit 29 (1999), S. 223-237 
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    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Zu den faszinierendsten “Waffen” im Tierreich gehören die Gifte. Auch viele Insekten setzen Gifte ein, zum Beispiel als Wehrgifte, wie sie von den staatenbildenden sozialen Hymenopteren, den Bienen, Hornissen und Faltenwespen bekannt sind. Die Wirkung dieser Gifte ist aufgrund ihrer medizinischen Bedeutung bereits intensiv untersucht. Über die Art und Weise der Giftinjektion sowie die Wirkungsweise der Gifte solitär lebender Wespenarten, etwa von Weg- und Grabwespen, ist vergleichs weise wenig bekannt. Eine Besonderheit der solitären Wespenarten ist, daß ausschließlich ihre Weibchen Insekten oder Spinnen jagen, um ihre künftige Brut zu versorgen. Spezielle jagdstrategien verringern dabei die Gefahr, daß potentielle Beutetiere die jagenden Wespenweibchen früch zeitig entdecken. Ist ein Beutetier optisch und/oder chemisch identifiziert. wird es je nach Wespenart durch einen oder mehrere Stiche paralysiert (gelähmt). Anfängliches Abwehrverhalten, selbst größerer Beutetiere, wird auf diese Weise unterbunden, und die Opfer können an einen sicheren Ort, ein Nest oder eine umfangreiche Nestanlage mit günstigem Mikroklima, gebracht werden, wo anschließend ein Ei abgelegt wird. Die sich auf ihrem Wirt entwickelnde Larve ist so vor dem Zugriff durch Feinde geschützt.Die an der Beute als Folge eines Stiches zu beobachtenden Giftwirkungen reichen von der vollständigen Paralyse, also dem totalen, in einigen Fällen auch irreversiblen Verlust der Fähigkeit, such zu bewegen, über vielfähigkeit, sich zu bewegen, über vielfältige, durch sas Gift bewirkte auffällige Verhaltensänderungen. Im Hinblick auf das Nervensystem lassen sich peri pher und zentral wirkende Gifte unter sscheiden, wobei der Wirkort durch das Stechverhalten der Wespe vorgegeben sein kann.
    Additional Material: 8 Ill.
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  • 190
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    Biologie in unserer Zeit 29 (1999), S. 256-256 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: No Asbstract.
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  • 191
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    Biologie in unserer Zeit 29 (1999), S. 260-260 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
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  • 192
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    Biologie in unserer Zeit 29 (1999), S. 268-277 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Additional Material: 18 Ill.
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  • 193
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    Biologie in unserer Zeit 29 (1999), S. 292-300 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Zu en vielen Schutz- und Verteidigungsstrategien, die von den Organismen entwickelt wurden, um dem Gefressenwerden zu entgehen, Zählen ein sperrigerwerden der Individuen, die Bildung von Panzern, Stacheln und Dornen, das Produzieren und Speichern von schwerverdaulichen Stoffen und Giften, aber auch die Entwicklung eines komplexen verhaltensrepertoires zur Vermeidung von Freßfeinden ‘8’. Bis zur dieses Jahrhunders glaubte man, daß die der Verteidigung dienenden Maßnahmen dauerhaft seien, also im Laufe der Evolution entstanden sind und im Verlauf ddes Lebens eines Individuums zu einem bestimmten Zeitpunkt zur Ausprägung, gelangen, unabhängig von der gerad herrschenden Bedrohung. Heute wissen wir, daß neben einer solchen kionstitutiven Verteidigung in vielen Organismengruppen auch induzierbare Verteidigungsmechanismen existieren, welche nur dann wirksam werden wenn Freßfeinde im Biotop in größerer Dchte auftreten und somit eine ernstzunehmende Bedrohung darstellen. Das Spektrum induzierbarer Feindabwehrmechanismen ist der Palette der kionstitutiven Abwehrmaßnahmen dabei durchaus sehr ähnlich. Der entscheidende Unterschied ist jedoch der, daß der bedrohte Organismus erst auf ein bestimmtes Signal hin von seinem genetisch festgelegten Schutzmechanismus Gebrauch macht. Dadurch werden die Kostenfür die Feindabwehr minimiert. Neben physikalischen Signalen (wie Licht und Temperatur), welche dem Organismus indirekt Auskunft über den Grad einer aktuellen Bedrohung geben können, spielen von den Freßfeinden abgegebene chemische Signale (Kairomone) eine entscheidende Rollen als Auslöser der induzierbaren Verteidigungsmechanismen. An der Aufklärung der chemischen Natur der Kariomione wird zur Zeit intenxiv gearbeitet.
    Additional Material: 8 Ill.
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  • 194
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    Biologie in unserer Zeit 29 (1999), S. 307-307 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
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  • 195
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    Biologie in unserer Zeit 29 (1999), S. 309-309 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Seit 1989 organisieren die beiden Zoologen Prof. Dr. H. K. Schminke aus Oldenburg und Prof. Dr. W. Westheide aus Osnabrück im Sommer einwöchige Intensivkurse zur Vermittlung taxonomisch-ökologischer Kenntnisse über einheimische Tiergruppen. BIUZ wollte mehr über diese Kurse und ihre Ziele wissen.
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  • 196
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    Biologie in unserer Zeit 29 (1999), S. V 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
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  • 197
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    Biologie in unserer Zeit 29 (1999), S. XII 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
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  • 198
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    Biologie in unserer Zeit 29 (1999), S. 318-318 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 199
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    Biologie in unserer Zeit 29 (1999), S. 336-345 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: In den letzten Jahren wurden immer mehr RNA-Editingprozesse entdeckt, welche die Abfolge der Nukleotidbausteine einer RNA nach der Abschrift aus dem zugehörigen Gen variieren. Mit der modifizierten Sequenz der Nukleotide ändert sich natürlich auch der Informationsgehalt der RNA - eine Proteinsequenz ist damit in diesen Fällen nicht mehr vollständig aus der DNA-Sequenz vorhersagbar. Teilweise verändert sich ein RNA-Molekül durch Editing so sehr, daß der Zusammenhang zwischen RNA und dem entsprechenden Gen in der DNA überhaupt nicht mehr zu erkennen ist.Inzwischen sind bei vielen verschiedenen Eukaryoten viele Spielarten des RNA-Editing bekannt. RNA-Editing kann einzelne oder mehrere Nukleotide einfügen und andere entfernen. Manche reife “richtige” mRNA ist in Trypanosomen nach dem RNA-Editing mehr als doppelt so lang wie die ursprüngliche Kopie des Gens. In anderen Fällen, insbesondere bei den höheren Eukaryoten von Moos bis Maus, verändern Desaminierungsreaktionen einzelne Basen in ihrer Identität. An spezifischen Orten einer RNA entsteht dabei aus einem Cytidin ein Uridin oder aus einem Adenosin- ein Inosinnukleotid. Sind diese Veränderungen in den mRNA-Editing in den mitochondrialen mRNAs der Pflanzen zur Regel. Hier ist praktisch jede mRNA vom RNA-Editing betroffen, das die vererbte Information an bis zu 1000 Positionen in den mRNAs korrigiert.
    Additional Material: 5 Ill.
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    Biologie in unserer Zeit 29 (1999), S. 371-371 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Additional Material: 2 Ill.
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