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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 41 (1985), S. 265-266 
    ISSN: 1420-9071
    Keywords: Rat ; hydrochlorothiazide ; pain threshold ; antinociceptive activity ; analgesic activity ; morphine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Hydrochlorothiazide, acutely injected in rats, has a weak analgesic activity per se and potentiates and prolongs the antinociceptive effect of morphine.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 63 (1985), S. 868-876 
    ISSN: 1432-1440
    Keywords: Distal nephrons ; Cellular heterogeneity ; Electrolyte excretion ; Furosemide ; Rat ; Kidney morphology ; Distale Nephrone ; Zelluläre Heterogenität ; Elektrolytausscheidung ; Furosemid ; Ratte ; Nierenmorphologie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die distalen Tubuli in der Nierenrinde gliedern sich nach der Macula densa in drei morphologisch verschieden gebaute Abschnitte: in die pars convoluta des distalen Tubulus (DCT), den Verbindungstubulus (CNT) und das corticale Sammelrohr (CCD). In den drei Segmenten sind insgesamt vier Zelltypen vorhanden: die DCT-Zelle, die CNT-Zelle, die Haupt-Zelle (P-Zelle) und die Schaltzelle (I-Zelle), die sich unter anderem an Hand der Ausbildung ihrer Zellmembranfläche unterscheiden lassen. In der DCT-, CNT- und P-Zelle ist in verschiedenem Ausmaß jeweils die basolaterale Membranfläche vergrößert, in der die Na-K-ATPase lokalisiert ist. In der I-Zelle ist die luminale Zellmembran vergrößert, in der wahrscheinlich eine H+-ATPase vorhanden ist. Bei längerdauernden Änderungen im Elektrolythaushalt treten in den Zellen strukturelle Anpassungserscheinungen auf, die vor allem das Ausmaß der aktiv transportierenden Membranflächen betreffen (basolaterale Membranflächen in DCT-, CNT- und P-Zellen; luminale Membran in I-Zellen). Die Veränderungen der basolateralen Membranfläche verhalten sich proportional zu den Änderungen der Na-K-ATPase-Aktivität und zeigen daher eine entsprechende Änderung der transzellulären Transportkapazität an. Morphologische Untersuchungen haben gezeigt, daß jeder Zelltyp nur auf für ihn spezifische Veränderungen im Elektrolythaushalt reagiert und erlauben daher gewisse Rückschlüsse auf die spezifische Rolle der einzelnen Zelltypen bei der Regulierung des Elektrolytausscheidung. Aus dem Muster der strukturellen Veränderungen läßt sich ableiten, daß bei bestimmten Zelltypen außer Hormonen offenbar auch die Elektrolytzusammensetzung der Tubulusflüssigkeit den transzellulären Transport beeinflußt. Daher müssen Veränderungen des Elektrolyttransports, die in einem Abschnitt spezifisch induziert werden (z.B. durch Furosemid), sich auch in nachgeschalteten Abschnitten auf den transzellulären Transport auswirken. Die zelluläre Heterogenität der distalen Abschnitte scheint eine differenzierte Regulierung der Elektrolytausscheidung unter unterschiedlichsten Bedingungen zu garantieren.
    Notes: Summary The distal segments beyond the macula densa — distal convoluted tubule, connecting tubule, cortical collecting duct — display cellular heterogeneity. The four different cell types, namely the DCT cell, CNT cell, the principal cell and intercalated cell differ mainly by the pattern of membrane amplification and they reveal also qualitative differences as to some cytoplasmic proteins. Each of the four cell types adapts to chronic changes in electrolyte metabolism with structural alteration, concerning essentially the membrane area over which the active transport step of the cell proceeds, in DCT-, CNT- and P-cells the basolateral cell membrane with the Na-K-ATPase, in intercalated cells the luminal cell membrane with a H+ ATPase. Since each cell type responds only to specific conditions with changes in membrane area and associated transcellular transport activity, morphological studies can help to determine the specific role of each cell type in the regulation of renal electrolyte excretion. Such investigations demonstrated that besides mineralocorticoid hormones the transport capacity of certain cells should depend on the solute composition of tubular fluid. Thus, changes in the transport pattern specifically induced in only one segment alters also the transport patterns of segments downstream. Cellular heterogeneity seems to guarantee the optimal regulation of renal electrolyte excretion.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 85 (1985), S. 178-183 
    ISSN: 1432-2072
    Keywords: Δ9-THC stimulus ; Δ9(11)·THC ; THC receptor ; Drug response ; Blockage of drug discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained in a water maze to discriminate between IP injections of 3 mg/kg Δ9- (Δ9(11)-THC) and its vehicle. Both Δ8- and Δ9(11) were generalized to the training drug. In contrast to our observations in rhesus monkeys, where Δ9-THC is at least 100 times less potent than Δ9-THC, Δ9(11) was found to be only seven times less potent in the rat. Relative potencies, expressed as the dosage at which 50% of the animals gave drug responses (ED50) were 1.8 mg/kg and 12.2 mg/kg for Δ9-THC and Δ9(11) respectively. Twenty-four hours after receiving 7×ED50=12 mg/kg Δ9 the tests showed intermediate results when conducted with the training dosage; 4×ED50=50 mg/kg Δ9-THC 48 h prior to the training dosage of 3 mg/kg Δ9-THC completely blocked drug-appropriate responses. Coinjection of ED50 dosages of Δ9- and Δ9(11)-THC led to 90% drug responses, demonstrating the additivity of the cannabis-like effect of both cannabinoids. Differences in the individual sensitivity of the rats to the tested cannabinoids were observed. Findings are interpreted in terms of the receptor mechanism for cannabis-like activity.
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  • 4
    ISSN: 1432-2072
    Keywords: Neurotensin ; Ventral mesencephalon ; Investigatory behaviour ; Motor behavior ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present experiments examined in detail the behavioral response to microinfusions of neurotensin (NT) into the ventral tegmental area (VTA), substantia nigra (SN) and hippocampus (HPC). The behavioral apparatus consisted of an eight-hole box in which investigatory and spontaneous motor behavior were recorded. Three doses (0.175, 0.5, 4.0 μg) of NT were injected into the VTA. The main effect of NT was a strong augmentation of rearing (frequency and duration) both in the periphery and center of the arena, accompanied by a small increase in locomotion and decreased grooming. NT had no effect on the strategy, organization, or duration of exploration but did augment frequency of hole visits towards the end of the session. NT injected into the SN and HPC had no effect on investigatory and spontaneous behavior with the exception of an increase in peripheral locomotion after HPC-NT injections. The results are discussed in terms of a modulatory role of endogenous NT on mesolimbic dopamine neurons.
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  • 5
    ISSN: 1432-2072
    Keywords: Opiates ; Nucleus accumbens ; Supersensitivity ; Chronic neuroleptic ; 6-OHDA lesion ; Mesolimbic dopamine neurones ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study the functional relationship between enkephalinergic and dopaminergic neurones at the level of the nucleus accumbens was investigated. The study consisted of two experiments in which dopaminergic (DA) transmission was chronically inhibited, and the behavioural locomotor response to intra-accumbens opiate injections analysed. First, specific 6-OHDA lesion of the DA-A10 neurones (either in nucleus accumbens or ventral tegmental area) was found markedly to increase the behavioural excitatory effects induced by nucleus accumbens injection of opioid peptides or morphine. Specific lesion of the central noradrenergic neurones had no such effect. Second, chronic pharmacological blockade of DA activity either with reserpine or a neuroleptic (pipothiazine palmitate) similarly induced a strong enhancement of the behavioral response to intra-accumbens opiate injection. The results are discussed in terms of novel mechanisms underlying denervation supersensitivity, and may have important implications for the relation between dopamine dysfunction in mental illness and opiate addiction.
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  • 6
    ISSN: 1432-2072
    Keywords: Dopamine ; Apomorphine ; Rotation ; Locomotor activity ; Stereotypy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Administration of drugs that reduce the influence of dopamine at its receptor site can lead to postsynaptic supersensitivity, whereas treatment with dopamine (DA) agonists can cause postsynaptic subsensitivity. Both unaltered and enhanced postsynaptic responses to DA have been shown after pretreatment with DA agonists. In the present manuscript pretreatment with apomorphine, a dopaminergic agonist, is shown to induce either increased or reduced locomotor activity. When a drug-free period between successive injections was allowed, apomorphine induced an enhanced locomotor response, whereas a reduced response occurred when each dose was injected before the previous apomorphine dose had been completely metabolized. Pretreatment with both high (1 and 3 mg/kg) and low (0.05 mg/kg) apomorphine doses enhanced the response. Apomorphine treatment that caused enhanced locomotor responses did not modify the stereotypy response to the drug. Similar enhanced or reduced response were found in rats with partial lesions of the nigrostriatal system. These altered responses to DA agonists may have important clinical consequences. The present data also suggest the existence of a different DA systems for locomotor and stereotypy actions of dopaminergic agonists.
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  • 7
    ISSN: 1432-2072
    Keywords: 8-OH-DPAT ; Feeding ; Locomotion ; Stereotypy ; Serotonin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of the putative serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on food intake in non-deprived male rats were investigated. Low doses of 8-OH-DPAT (15–60 μg/kg) significantly increased food intake, without affecting drinking, grooming, rearing or locomotion. Microstructural analysis of the elicited feeding behaviour revealed that the rate of eating after 8-OH-DPAT treatment was very similar to that previously reported following 16 h food deprivation. Higher drug doses (250–4,000 μg/kg) also elicited feeding and caused locomotor stimulation and serotonin-related stereotyped behaviour (i.e. forepaw padding, headweaving, wet dog shakes, flat body posture). When feeding and stereotypy were observed concurrently, response competition was evident and feeding behaviour was fragmented into numerous short eating bouts. As drug-induced stereotypy declined with time, this fragmented pattern of eating was succeeded by long bouts of eating which were similar to those observed at doses of 15–60 μg/kg 8-OH-DPAT. The induction of feeding by a serotonin agonist appears paradoxical, since drugs which enhance brain serotonergic activity usually inhibit feeding.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 86 (1985), S. 344-347 
    ISSN: 1432-2072
    Keywords: β-Carboline ; Benzodiazepines ; Anxiety ; Food intake ; Aggression ; FG 7142 ; Pentylenetetrazol ; Caffeine ; Lactation ; Maternal behaviour ; Sex hormones ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mother rats nursing large litters are hyperphagic, aggressive towards conspecifics, and show less freezing behaviour than non-maternal animals. These naturally occurring adaptations resemble those elicited by benzodiazepine treatment in virgin rats, indicating a common neurochemical change in the brains of mother rats and benzodiazepine-treated virgins. In line with this hypothesis, it was found that three functional benzodiazepine antagonists (FG 7142, pentylenetetrazol, caffeine) decreased food intake, lowered aggression and strengthened freezing in lactating mother rats. These psychopharmacological observations support the idea that GABA neurotransmission is enhanced during motherhood in the rat.
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  • 9
    ISSN: 1432-2072
    Keywords: Acetylcholinesterase ; Acetylcholinesterase inhibitors ; Soman ; Schedule-controlled behavior ; Fixed interval ; Gastrointestinal tract ; Brain ; Tolerance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intraperitoneal (IP) administration of the acetylcholinesterase inhibitor, soman (10–40 μg/kg), suppressed in a dose-related manner response rates in rats maintained under a multiple fixed-interval 50-s fixed-ratio 25 schedule of food delivery. Chronic administration of soman at weekly intervals resulted in tolerance to the response. When soman administration was separated by 2–5 weeks in individual rats, the suppressive effects of the agent again became apparent. Analysis of acetylcholinesterase activity revealed that enzyme inhibition was limited to gastrointestinal areas near the site of injection. There was no significant effect on brain acetylcholinesterase even following IP injection of doses which completely suppressed responding. The IP route may be useful for studying tolerance and other chronic effects of soman without producing generalized toxicity.
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  • 10
    ISSN: 1432-2072
    Keywords: Imipramine ; Hippocampus ; Apomorphine ; Dopamine ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of apomorphine, injected into the dorsal hippocampus, on the locomotor activity of imipraminetreated rats was studied. The rats were chronically implanted with cannulae 1 week before imipramine treatment. Imipramine was given in a dose of 10 mg/kg per os, acutely, or twice a day for 14 days. Intrahippocampal injection of apomorphine induced a dose-dependent increase in locomotor activity. This effect was antagonized by pretreatment with pimozide (2 mg/kg). Repeated, but not single, administrations of imipramine significantly enhanced the apomorphine-induced locomotor hyperactivity in rats. This effect was observed at 2, 48 and 96 h after the last dose of imipramine. The results obtained indicate that repeated administration of imipramine increases the responsiveness of the hippocampal dopaminergic system.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 85 (1985), S. 31-36 
    ISSN: 1432-2072
    Keywords: Promethazine ; Nociception ; Antinociception ; Dose-response ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study demonstrates that low doses of promethazine (1.25–5 mg/kg SC) dose-dependently facilitate nociception in the vocalization test in rats. However, this effect disappeared gradually with increasing dose, and in contrast, high doses (20–40 mg/kg SC) induced an antinociceptive effect. This indicates that promethazine, depending upon the biophase concentration, has the potential to interact with separate antagonizing or opposing functional systems, producing contrasting effects on nociception. The sigmoid E max model was fitted to the observed composite effect, and dose-response characteristics for two opposite effects were described. In addition, when suprathreshold stimulation was used to evoke nociception, the stimulus amplified the hyperalgesic efficacy of promethazine but left the potency of this effect unaltered. In this experimental situation only negligible antinociception was observed. Our data thus show that for promethazine, the net effect on nociception in rats is not absolute but is balanced both by the biophase concentration and by the effectiveness of the stimulation used to evoke nociception.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 85 (1985), S. 80-86 
    ISSN: 1432-2072
    Keywords: Conditioned suppression ; Drug stimuli ; Stimulus control ; Overshadowing ; Classical conditioning ; Operant behavior ; Drugs ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to press a lever under a variable-interval (VI) schedule of water reinforcement. After stable responding had developed, a 4.5-KHz tone (CS) was conditioned classically to a 2.5-mA electric shock (US) in groups of animals which had been given various psychoactive drugs or saline. Twenty-four hours later, a stimulus generalization test was conducted in the absence of drug; during this session, tones that varied in frequency around 4.5 KHz were presented while the animals were responding under the VI schedule. In animals conditioned under saline, all tones (non-differentially) suppressed responding which, however, recovered gradually over time. This suppressive effect was eliminated by lysergic acid diethylamide (LSD; 0.2 and 0.32 mg/kg), cocaine (20 mg/kg), diazepam (2.5 mg/kg), lisuride (0.08 mg/kg), mescaline (20 mg/kg) and 5-methoxy-N,N-dimethyltryptamine (4 mg/kg), and was attenuated by amphetamine (4 mg/kg), pentobarbital (15 mg/kg) and morphine (4 mg/kg). Atropine (10 mg/kg), scopolamine (1 mg/kg), clonazepam (0.5 mg/kg), and chlorpromazine (4 mg/kg) did not alter the suppressive effect of the tone. The serotonin antagonist BC-105 (6 mg/kg) reversed the effect of 0.2 mg/kg of LSD. These results suggest (1) that drug-induced stimuli may “overshadow” other (e.g., external) stimuli during classical conditioning and, (2) that drugs might affect behavior by altering processes (stimulus control or others) that do not simultaneously involve response or motor control.
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  • 13
    ISSN: 1432-2072
    Keywords: Clonidine ; Sedation ; Activity ; RHA/iop and RLA/iop ; Strains ; Adrenoceptors ; Stress ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An hypothesis that repeated stress results in central changes in α2-adrenoceptor sensitivity was investigated using a behavioural test. Stressed (immobilisation for 2 h/day for 7 days) and unstressed rats from the RHA/iop and RLA/iop strains were tested for the sedative effects of the α2-adrenoceptor agonist clonidine on Y-maze behaviour. The measures used were number of lines crossed, arm entries and rearing. The stressed animals showed higher scores for line crossings and rearing; but the only significant difference between the strains was for rearing, which was higher for RHA/iop. Clonidine significantly depressed all the measures of activity. However, there was no evidence of an interaction of the drug with stress for any of the measures. It is concluded that neither repeated stress nor genetic differences in the ability to cope with stress influence the behavioural effects of clonidine. This suggests that stress responses are not related to the central α2-adrenoceptor system.
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  • 14
    ISSN: 1432-2072
    Keywords: Amphetamine ; Haloperidol ; Dopamine ; Y-Maze ; Alternation ; Rearing ; Collateral behaviour ; “Switching” ; Novelty ; Attention ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The degree of alternation of arm choice in a Y-maze was examined on 15-min tests over 4 days in rats treated (IP) with saline, amphetamine (0.5 or 2.0 mg/kg) or pretreated with haloperidol (0.08 mg/kg) in each condition prior to test. On day 1 amphetamine-treated animals chose arms at random, but from day 2–4 those receiving the higher dose perseverated their choice. Controls maintained alternation. These effects could be prevented by haloperidol pretreatment. Amphetamine treatment increased the frequency of rearing at the middle, choice-point of the maze more than at the end of an arm. The increase at the mid-point was suppressed by haloperidol pretreatment from day 1 and at the end of an arm from day 2. Amphetamine induced an increase in head-turning/“looking” that was suppressed by haloperidol from day 2. The effect of haloperidol in increasing the duration of an item of looking or rearing at the end of an arm also started later in testing. Two effects are postulated to have occurred: (i) a conflict on day 1 between novelty-controlled sensory or attentional effects that leads to an alternation of arm choice and amphetamine-induced dopaminergic activity that facilitates an alternation of behavioural responses. The result was random choice and increased rearing at the choice point. (ii) On days 2–4 the drug-induced effects on switching motor responses came to control behaviour.
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  • 15
    ISSN: 1432-2072
    Keywords: d-Amphetamine ; Response rate ; Reinforcement efficacy ; Response topography ; Matching law ; Rate-dependency ; Variable-interval schedule ; Lever press ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A mathematical model was used to describe the effects of amphetamine on the rate of a reinforced response in the rat. The model provides measures of reinforcement efficacy and response topography for behavior maintained by variable-interval reinforcement schedules. In this study the measured behavior was a lever press, the reinforcer was water, and the variable-interval schedules provided five different rates of reinforcement, ranging from about 20 to 660/h. In each session the rats were exposed to each of the five schedules, and as reinforcement rate increased, the rate of lever pressing increased in a negatively accelerated manner that was closely approximated by the equation for a rectangular hyperbola. Amphetamine changed responser rate and the parameters of the best-fitting hyperbolas. The 0.25–1.0-mg/kg doses increased response rate, and the parameter changes supported the interpretation that the increases were due primarily to an increase in reinforcement efficacy. The 2.0- and 3.0-mg/kg doses decreased response rates maintained by low reinforcement rates and increased response rates maintained by high reinforcement rates, and the parameter changes supported the interpretation that at higher doses amphetamine produced counteracting changes in reinforcement efficacy and response topography: reinforcement efficacy decreased, whereas response topography changed so as to increase response rates.
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  • 16
    ISSN: 1432-2072
    Keywords: γ-Aminobutyrate (GABA) ; GABA and GABA agonists ; Chlordiazepoxide ; Amylobarbitone ; Picrotoxin ; Bicuculline ; β-Carbolines ; Muscimol ; Baclofen ; Punished barpressing ; Anxiety ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to press a bar for sucrose reward on a random-interval (RI) schedule and footshock punishment was then introduced for 3-min intrusion periods (signalled by a tone) on an independent RI schedule. Shock intensity was individually adjusted to produce stable intermediate levels of response suppression during the tone for each animal. Groups of animals were then allocated to a number of separate experiments in which they were systemically injected with anxiolytics (chlordiazepoxide HCl or sodium amylobarbitone), GABA antagonists (picrotoxin or bicuculline), the GABAA agonist muscimol, the GABAB agonist baclofen, an antagonist (RO 15-1788) at the benzodiazepine receptor and, an inverse agonist (FG 7142) at this receptor. The results showed that the alleviation of punishment-induced suppression of barpressing produced by chlordiazepoxide was blocked or partially blocked by RO 15-1788, picrotoxin and bicuculline but not by FG 7142; that picrotoxin (but not FG 7142) increased the suppression of responding by punishment; that neither muscimol nor baclofen affected responding on their own, but their combination weakly but reliably released punished responding from suppression; and that the anti-punishment effect of amylobarbitone was unaffected by either picrotoxin or bicuculline, though the barbiturate reversed the punishment-enhancing effect of picrotoxin. These results are discussed in the light of the hypothesis that anxiolytic behavioural effects are due to increased GABAergic inhibition.
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  • 17
    ISSN: 1432-2072
    Keywords: Heroin ; Intravenous self-administration ; Methyl naloxonium chloride ; Opiates ; Reward ; Nucleus accumbens ; Ventral tegmental area ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A quaternary derivative of naloxone, methyl naloxonium chloride (MN), was administered intracerebrally to rats trained to self-administer heroin intravenously. Increases in intravenous (IV) heroin self-administration rates were found following injections of low doses of MN into the nucleus accumbens (N.Acc), but not following injections of low doses of MN into the ventral tegmental area (VTA). These results were interpreted to suggest that the rewarding properties of IV heroin were decreased following N.Acc opiate receptor blockade. The relative insensitivity of the VTA to MN treatment was taken to suggest that VTA opiate receptors are either not essential or play a secondary role in mediating IV heroin self-administration. The present data support the notion that post-synaptic N.Acc opiate receptors play a crucial role in maintaining IV heroin self-administration.
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  • 18
    ISSN: 1432-2072
    Keywords: Substance P ; Ventral mesencephalon ; Investigatory behavior ; Motor behavior ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present experiments the behavioral response to substance P (SP) microinfusion into the ventral tegmental area (VTA), substantia nigra (SN), and sensorimotor cortex (CX) was investigated in detail. The experiments were carried out using an eight-hole box to measure exploratory behavior and a video monitor for the analysis of spontaneous motor behavior. When infused into the VTA, SP (0.125, 0.5, 3.0 μg) augmented the frequency and total duration of hole-pokes, and tended to diminish the mean duration of hole-pokes. The strategy and organization of responses, as measured by the order of hole-visits and hole-switching, were unchanged by SP and there was no indication of stereotypy, measured by the number of hole-pokes per hole-visit. The open-field analysis revealed a marked increase in locomotion and rearing, both in the periphery and center of the arena; grooming was decreased by SP. The behavioral profile following SN infusions of SP (3.0 μg) was similar to that elicited by VTA infusions, with the exception that center rearing was not enhanced. SP administration into cortex (3 μg) had no significant effect on any behavioral measures. It is hypothesized that SP infused into the ventral mesencephalon results in an enhancement of approach response tendencies, suggesting that endogenous SP in this region may regulate spontaneous behavior. The possibility of an interaction between SP and meso-telencephalic dopamine neurons is discussed.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 85 (1985), S. 464-468 
    ISSN: 1432-2072
    Keywords: Dopamine agonist ; Lisuride ; Apomorphine ; Locomotor activity ; Serotonin agonist ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The open-field test was used to study the involvement of serotonergic and dopaminergic mechanisms in the action of lisuride on locomotor activity in the rat. Lisuride produced a biphasic locomotor effect. The maximum locomotor stimulatory response of lisuride was stronger than that of apomorphine and comparable with that of apomorphine and LSD combined. Hypermotility induced by high doses of lisuride was partially suppressed by the serotonin antagonist cyproheptadine and not further enhanced by LSD. A moderate dose of lisuride potentiated apomorphine-induced hypermotility in the same manner as has been shown for LSD. Lesion of dopaminergic structures within the median raphe nucleus by 6-OHDA produced a potentiation of lisuride-induced hypermotility. This effect was suppressed by cyproheptadine. The locomotor inhibitory effect of low doses of lisuride may be related to a stimulation of presynaptic mesolimbic dopamine receptors. It is concluded that the locomotor stimulant effect of higher doses of lisuride may depend on stimulation of postsynaptic dopamine receptors and a scrotonergic action and that the locomotor effects of lisuride reflect a complex interaction at dopaminergic and serotonergic transmission systems.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 85 (1985), S. 483-485 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Stimulus control ; Benzodiazepine antagonist ; Ro 15-1788 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The imidazodiazepine Ro 15-1788 is a proposed benzodiazepine receptor antagonist. Recently however, behavioural effects of Ro 15-1788 have been demonstrated. In the present study, rats (n=12) were trained to discriminate Ro 15-1788 (10 mg/kg, IP, t=15 min) from vehicle in a two-lever food-reinforced procedure. All rats showed a reliable discrimination (mean injection-appropriate lever responding 〉85%) after about 60 daily training sessions. Drug stimulus control was evidenced by an orderly generalization gradient obtained with 0.01–30 mg/kg Ro 15-1788 (ED50 for stimulus generalization: 0.12 mg/kg). Since even low doses of Ro 15-1788 have discriminative effects in the rat, it is concluded that Ro 15-1788 may have potent behavioural activity.
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  • 21
    ISSN: 1432-2072
    Keywords: d-Amphetamine ; Operant behaviour ; Variable-interval schedules ; Herrnstein's equation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dose-response curves were obtained for the effects of d-amphetamine sulphate (0.1–3.2 mg/kg) on the operant performance of rats in variable-interval 4-min and variableinterval 20-min schedules of reinforcement. Response rates maintained under variable-interval 4-min were suppressed in a dose-dependent manner. Response rates maintained under variable-interval 20-min schedules tended to be elevated by low doses and suppressed by higher doses. The degree of response rate suppression was greater in the case of the variable-interval 4-min schedule. The results are consistent with the previously reported effect of d-amphetamine on the values of the two constants of Herrnstein's (1970) equation: the drug reduces the reinforcement frequency needed to maintain the half-maximum response rates (K h) and lowers the maximum response rate (R max) (Bradshaw et al. 1981 b). It is suggested that the effects of d-amphetamine on operant performance may involve two processes: an enhancement of motivation and a reduction of the capacity to respond.
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  • 22
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    Psychopharmacology 87 (1985), S. 219-224 
    ISSN: 1432-2072
    Keywords: Propranolol ; Beta-adrenergic blocker ; Differential reinforcement of low rates of response (DRL) ; Differential punishment of high rates of response (DPH) ; Chlordiazepoxide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ten rats were trained to lever press for food reward on a schedule of differential reinforcement of low rates of response with a 20-s criterion (DRL 20). Ten more were trained on a new schedule of punishment, designed to be comparable to DRL 20 — differential punishment of high rates of response (DPH 20). Under this schedule, responses with a latency of 20 s or more earned food rewards, while those of less than 20 s were followed by food reward and brief electric footshock. After 42 sessions, rats on each schedule showed temporal discrimination in the distribution of inter-response times. The effects on these baselines of the anxiolytic chlordiazepoxide (CDP; 1 mg/kg IP) and the beta-blocker propranolol (2, 5 and 10 mg/kg IP) were investigated. Both drugs reduced numbers of responses reaching criterion (criterion resonses) in DPH, CDP increasing total responses. CDP acted similarly under DRL, but propranolol only affected performance at the highest doese, which reduced criterion responses, probably because of changes in total responding. Each drug increased response bursts. It is concluded that propranolol can exert a disinhibitory action in these schedules, although with some differences from that of the benzodiazepine CDP.
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  • 23
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    Psychopharmacology 87 (1985), S. 260-265 
    ISSN: 1432-2072
    Keywords: Active avoidance ; Nociception ; Spinal serotonin ; p-Chloroamphetamine ; 5,6-Dihydroxytryptamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of selective lesions of the descending serotonergic (5-HT) pathways on analgesia and avoidance deficit induced by the 5-HT releasing compound p-chloroamphetamine (PCA, 2.5 mg/kg) were investigated in male rats. Intrathecal injection of 5,6-DHT (20 μg/rat) reduced the uptake of labelled 5-HT into spinal synaptosomes by approximately 85% but did not significantly affect the uptake of noradrenaline. The lesions produced a significant hyperalgesia and strongly attenuated the analgesic effect of PCA in the hot-plate test. In the flinch-jump test 5,6-DHT lesioned rats receiving PCA did not differ from the saline control group. Spinal lesioning did not, however, affect one-way active avoidance performance and did not prevent the marked impairment of avoidance performance induced by PCA. Thus, the avoidance deficit caused by PCA is independent of the descending serotonergic pathways and of the analgesia induced by PCA. These results support the view of a differential involvement of the ascending and descending serotonergic projections in behavioural processes controlled by aversive stimuli.
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  • 24
    ISSN: 1432-2072
    Keywords: Dopamine ; Acetylcholine ; Acute dystonia ; Peri-oral behaviour ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Continuous administration of haloperidol, sulpiride, or cis-flupenthixol, but not of domperidone or apomorphine, to Wistar rats for up to 3 weeks caused an increase in spontaneous purposeless chewing movements. Treatment with physostigmine and pilocarpine, but not neostigmine, for up to 3 weeks increased chewing, whilst scopolamine decreased chewing. Metergoline and cyproheptadine, but not quipazine, increased chewing after only 1 and 7 days but not thereafter. Chewing was not altered following treatment with compounds acting on GABA or noradrenaline systems or by a range of non-neuroleptic agents inducing dystonia in man. The enhancement of chewing induced by neuroleptic and cholinomimetic drugs was reduced by acute treatment with scopolamine, and reverted to control levels following drug withdrawal. Neuroleptic-induced purposeless chewing in Wistar rats appears to be primarily influenced by cerebral dopamine and acetylcholine function and may resemble acute dystonia, rather than tardive dyskinesia.
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  • 25
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    Psychopharmacology 85 (1985), S. 87-91 
    ISSN: 1432-2072
    Keywords: Schedule-induced polydipsia ; Rat ; Post-trial treatment ; β-endorphin ; Naloxone ; ACTH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of three experiments examined the possible involvement of endogenous opioid peptides in the development of schedule-induced polydipsia in rats. Repeated pretraining treatment with 2 mg/kg naloxone impaired acquisition of schedule-induced polydipsia, whereas the same treatment injected after training increased drinking. This later effect was time dependent, since a 30-min delay in the injection of naloxone resulted in a disappearance of its effect. Post-training injections of 10 μg/kg β-endorphin or ACTH delayed the development of drinking. These findings are consistent with the hypothesis that endogenous opioid peptides modulate the development of schedule-induced polydipsia.
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  • 26
    ISSN: 1432-2072
    Keywords: Cimetidine ; Rantidine ; Imidazole ; (±) NPA ; Penile erections ; Stretching and yawning ; Stereotyped behaviour ; DA receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cimetidine injected IP 15 min before (±) N-n-propylnorapomorphine (NPA) antagonized in dose-dependent fashion the penile erections (PE) and stretching and yawning (SY) induced by this typical dopaminergic agonist in male rats. Ranitidine, which acts on H2 histamine receptors in much the same way as cimetidine despite its lack of an imidazole ring, failed to produce the same effect. On the other hand, imidazole itself was similar to cimetidine in antagonizing PE and SY induced by (±) NPA, whether injected IP or ICV. Neither imidazole nor cimetidine antagonized the stereotyped behaviour (SB) induced by (±) NPA. Indeed, imidazole reduced the latency of this response. A mechanism which may underly these effects is discussed, as well as the possible preclinical use of this test in animals.
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  • 27
    ISSN: 1432-2072
    Keywords: 5-HT antagonist ; LSD antagonist ; Drug discrimination ; Anxiety ; 5-HTP ; Head twitch ; Conflict behavior ; Hypothermia ; Ritanserin ; Pirenperone ; Chlordiazepoxide ; Diazepam ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The newly synthesized compound and putative 5-HT2 antagonist ritanserin, but not the structurally related compound R 56413, resembles pirenperone in that it acts as a pure antagonist in an LSD-saline drug discrimination assay in the rat. Ritanserin exceeded pirenperone in terms of behavioral specificity; the lowest effective dose of ritanserin in antagonizing LSD was one order of magnitude higher than that of pirenperone, but the compound depressed rate of operant responding only at doses that were about 1000-fold higher than those at which pirenperone was effective. Ritanserin exerted effects in an open field test which were reminiscent of anxiolytic drug activity in the rat; its effects were greater than those of pirenperone, R 56413 and the benzodiazepines chlordiazepoxide and diazepam. The results of experiments on antagonism of 5-HT-induced hypothermia and of the 5-HTP-induced headtwitch response fail to support the possibility that the putative anxiolytic effects of ritanserin in the rat can be ascribed simply to a pharmacologically defined action at 5-HT receptors.
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  • 28
    ISSN: 1432-2072
    Keywords: CGS 8216 ; DMCM ; FG 7142 ; Food intake ; Midazolam ; Palatability ; Ro15-1788 ; Satiety ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Non-deprived rats were familiarised with a highly palatable diet until baseline consumption in a 60-min daily access period had stabilised. The benzodiazepine receptor agonist midazolam (1.25–10.0 mg/kg, IP) produced a large, dose-related increase in food consumption during the first 30 min of access. It also produced significant, short-term hyperphagia in animals which had been partially pre-satiated on the diet before drug administration, an effect which was reversible by the benzodiazepine receptor antagonist Ro15-1788. Administered alone, Ro15-1788 (1.25–10.0 mg/kg, IP) had no intrinsic activity in the food consumption test. In contrast, CGS 8216 (2.5–40.0 mg/kg, IP) produced a marked dose-related suppression of food intake. This anorectic effect was shared by two benzodiazepine receptor inverse agonists, FG 7142 and DMCM, which also produced dose-dependent reductions in consumption. The effects on feeding produced by FG 7142 (20 mg/kg, IP) and DMCM (1.25 mg/kg, IP) were reversed by either Ro15-1788 (2.5 and 5.0 mg/kg) or midazolam (5.0 and 10.0 mg/kg). A matched anorectic effect produced by CGS 8216 (40 mg/kg) was not, however, reversed by either Ro15-1788 or midazolam. This suggests that at a high dose CGS 8216 may act by a mechanism different from that of the two inverse agonists. The feeding test described in the report proved sensitive to both hyperphagic and anorectic effects of drugs active at benzodiazepine receptors, pointing to a possible bi-directional control of palatable food consumption.
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  • 29
    ISSN: 1432-2072
    Keywords: Ethanol ; Reinforcement ; Aversion ; Place conditioning ; Situational variables ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hypothesis was examined that the interaction of ethanol with the conditions under which it is administered may determine whether either preference or aversion for the drug develops. In Experiment 1, eight groups of food-deprived rats received injections of ethanol (175–1,400 mg/kg) in one environment and were later offered a choice between that environment and a different one previously associated with saline injections. Another eight groups were treated identically, except that food was available in both the saline and ethanol-paired environments. The groups given the drug without food showed no preference or aversion at low doses (175–700 mg/kg), but showed aversion at higher doses (1,000 and 1,400 mg/kg). When food was available, there was an increased preference for the environment paired with the 500 mg/kg doses. In Experiment 2, placing two rats together increased each rat's preference for the environment associated with the other animal. However, rats pretreated with 500 mg/kg ethanol before being placed together showed a reduced preference for the environment associated with the drug and the other animal. Controls never paired with another rat showed no preference or aversion at the same ethanol dose. Thus, ethanol may interact with conditions such as the presence of food or another animal to determine final effects that are unique to those conditions.
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  • 30
    ISSN: 1432-2072
    Keywords: 6-Hydroxydopamine ; Differential reinforcement of low rates of response (DRL) ; Sympathetic nervous system ; Noradrenaline ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract First, it was confirmed that systemic injection of the neurotoxin 6-hydroxydopamine HBr (30 mg/kg IP) depleted noradrenaline levels in rat heart, but not centrally. Losses averaged 90% of control 1 day after injection, and 50% at 42 days. The same drug and dose was then administered to 50% of a group of rats which had been trained to lever-press for food reward on continuous reinforcement (CRF). After further CRF sessions, the rats were changed to a schedule of Differential Reinforcement of Low Rates of Response with a 20-s criterion (DRL 20). The drugged rats earned fewer reinforcements during DRL than did controls, and made fewer responses. Temporal discrimination (shown by the IRT/Opp distribution) was disrupted. It is concluded that peripheral noradrenergic systems may be involved in the control over responding by temporal cues associated with reward and non-reward.
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  • 31
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    Psychopharmacology 87 (1985), S. 238-241 
    ISSN: 1432-2072
    Keywords: Conditioned taste aversion ; Vasopressin ; Vasopressin analogs ; Vasopressin antagonist ; Hypertension ; Apomorphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats injected SC with arginine vasopressin (AVP) following consumption of a milk solution developed a marked aversion to the taste of this solution. An analog of vasopressin devoid of pressor activity, dDAVP, was unable to induce conditioned taste aversion. The aversive stimulus properties of AVP were blocked by the vasopressor antagonist dPTyr(Me)AVP. This antagonist did not block apomorphine-mediated conditioned taste aversion. These results demonstrate that AVP induces conditioned taste aversion by interacting with vasopressor-like receptors.
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  • 32
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    Psychopharmacology 87 (1985), S. 225-232 
    ISSN: 1432-2072
    Keywords: Place conditioning ; Diazepam ; Meprobamate ; CGS 8216 ; Picrotoxin ; Sodium valproate ; Naloxone ; Reward ; Aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The place conditioning paradigm was used to examine the reinforcing properties of diazepam. Rats were injeccted with diazepam (0.5–5.0 mg/kg, IP) and 30 min later were confined for 30 min to one side of a shuttle box, in which each of the two compartments had distinctive features. On alternate (control) days they received vehicle injections and were confined for 30 min to the opposite side. At almost all doses tested, diazepam produced place preference for the distinctive compartment that had been previously associated with the drug. Preference for the drug side developed regardless of whether diazepam was paired or unpaired with the least-preferred side, and regardless of whether testing was carried out in the undrugged or in the drugged state. The rats preferred the drug side over a novel compartment, but they did not change their initial preference for the side when diazepam was given after removal from the training box. Animals injected with meprobamate (70 mg/kg, PO), a non-benzodiazepine anxiolytic, also developed conditioned preference for the drug side, comparable to that seen following cocaine hydrochloride (10 mg/kg, IP). The diazepam (2.5 mg/kg)-induced place preference was antagonized by CGS 8216 (3 mg/kg, IP), picrotoxin (2 mg/kg, IP) and naloxone (0.8 mg/kg, SC), injected 3 min before and 15 and 20 min after diazepam respectively. Sodium valproate (200 mg/kg, IP) did not influence diazepam (1 mg/kg)-induced place preference. Sodium valproate by itself had marginal effects on place conditioning. Picrotoxin and naloxone, but not CGS 8816, produced place aversion which, in the case of picrotoxin, was due to state dependent learning. The results provide a clear indication that the place preference paradigm is valid as a test for evaluating appetitive properties of minor tranquilizers. They suggest that the rewarding effects of diazepam are mediated through central benzodiazepine receptors. Wheter GABA and/or endogenous opioid peptides are involved in the reinforcing properties of diazepam remains an open question.
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  • 33
    ISSN: 1434-0879
    Keywords: PUVA ; Kidney transplantation ; Rat ; UV irradiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pretreatment of the kidney donor with 8-methoxypsoralen (8-MOP) and ex vivo longwave ultraviolet irradiation (UVA) of the kidney prolonged the subsequent survival on allogeneic recipients. The efficacy of this treatment seems to be dependent on the time and dose of UVA irradiation rather than on the dose of 8-MOP. In conclusion, PUVA treatment is effective in reducing the immunogenicity of the rat kidney allograft, although the mechanism remains unclear. These experimental findings are new and preliminary results in clinical human kidney transplantation are favourable.
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  • 34
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    Research in experimental medicine 185 (1985), S. 173-179 
    ISSN: 1433-8580
    Keywords: Biliary sepsis ; 125I-labeledE. coli ; Retrograde intrabiliary injection ; Biliary obstruction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 125I-labeledE. coli was injected into the biliary tree of normal rats and rats with 3 weeks' obstruction of the common bile duct to investigate the liver clearance capacity for bacteria. Bile was collected during 15 min, immediately, 1h, 4h, or 24h after the injection. Tissue specimens from the liver, lungs, spleen and kidneys, and blood and urine specimens were collected simultaneously. In normal rats, 40% of the bacteria was recovered in the bile immediately after the injection, whereas 30% was already trapped in the liver. Incubation of the bacteria in the bile duct for 1h, 4h, and 24h resulted in liver retentions of 43%, 15%, and 4%, respectively. The recovery in the bile was 13% after 1-h incubation, and further prolongation of the incubation did not result in a significant decrease. In contrast to these findings, 70% of the injected bacteria was retained in the biliary tree in rats with chronic biliary obstruction (P 〈 0.05 as compared to normal rats) and only 1% was trapped in the liver (P 〈 0.005) 15 min after injection. One-hour incubation of bacteria in the bile duct decreased the retention in the bile to 30%, but the retention in the liver increased only slightly in these animals. Four and 24h after injection less than 30% of the bacteria was retained in the hepato-biliary system. Most of these animals showed almost no radioactivity exceeding the background count in the blood, urine, spleen, lungs, and kidneys 15 min after injection. It was concluded that the impaired clearance capacity of the liver in chronic biliary obstruction might contribute to the susceptibility of such animals for bacteria introduced in the bile.
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  • 35
    ISSN: 1432-0568
    Keywords: Lipofuscin ; Alcohol-ageing ; Cerebellar interneurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lipofuscin deposition in nerve cells is one of the most reliable and consistent neurocytological features correlated with ageing. Purkinje cells of long-term alcoholfed rats show large agglomerates of lipofuscin granules after six months of alcohol experiment, whereas in normal biological ageing, this happens only after 25 months of age. Cerebellar interneurons have specific patterns of lipofuscin accumulation during ageing concerning both its morphological type and chronology of deposition. We studied the effects of chronic alcohol treatment on cerebellar interneurons taking particular account of lipofuscin pigment accumulation. Control and alcohol-fed groups for 1, 3, 6, 12 and 18 months were used. A precocious and progressive accumulation of lipofuscin granules occurred in granule, Golgi and basket cells. Stellate cells remained pigment-free. The lipofuscin deposited in the granule and Golgi cells was of the granular type, whereas that of basket and stellate cells was lamellar (fingerprint-like pattern). These results parallel those observed during normal ageing, and reinforce the hypothesis of the existence of a close relationship between chronic alcohol consumption and precocious nerve cell ageing.
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  • 36
    ISSN: 1432-0568
    Keywords: Rat ; Developing forebrain ; Immunocytochemistry ; Albumin ; Uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several plasma proteins are found within the cells of the developing brain of many species, with a distribution pattern which changes during development, but the origin of such proteins is in dispute. The experiments described here were designed to test the hypothesis that some developing brain cells are able to take up plasma proteins. The distribution of the plasma protein albumin has been studied in the rat forebrain from the 14th day of gestation until birth. Although present within the cerebrospinal fluid and plasma from the earliest age studied, albumin was not seen within cells of the developing forebrain until day 16E or 17E. A foreign protein, sheep albumin, was injected into the ventricles at days 14E, 16E, 18E, 20E and on the day of birth. Sheep albumin can be detected in the presence of rat albumin because the antibody to sheep albumin does not cross-react with rat albumin. The sheep albumin was taken up very rapidly into cells of the ventricular zone at the later but not the earlier ages, thus mimicking the distribution of the naturally occurring rat albumin. After the foreign albumin had been left within the ventricle for several hours, some of the cells of the cortical plate also contained the protein, again mimicking the normal distribution of albumin. These findings suggest that the presence of albumin within cells of the developing rat forebrain can largely be attributed to uptake rather than synthesis.
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  • 37
    ISSN: 1432-0568
    Keywords: Dopamine-β-hydroxylase ; Anterior column ; Ultrastructure ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dopamine-β-hydroxylase (DBH) immunohistochemistry was used to demonstrate the noradrenergic fibers and terminals in the anterior column of the rat lumbosacral spinal segments. PAP-positive varicose fibers were widely distributed in the gray matter with preferential accumulation in the nuclear regions containing motoneurons involved in the contraction of perineal striated muscles. Unmyelinated DBH fibers were composed of nodular enlargements (varicosities, 0.4–3.0 μm in diameter) and very fine, short intervals (intervaricose segments, 0.1–0.2 μm in diameter and 1.0–4.0 μm in length). DBH-positive dense products were electron microscopically often confined within small granular particles and less frequently within large granules. Additionally, in order to characterize the innervation pattern of noradrenergic fibers on dendritic bundles organized in the motoneuronal pools innervating the pelvic small muscles, semi-quantitative analysis was done in the area of the dorsolateral nucleus endowed with especially well-developed dendritic bundles. DBH terminals contacting with unreactive dendrites were more common (67.9%) than those with neuronal somata (15.1%), and the remainder (17%) had no contacts with surrounding neuronal elements. Furthermore, specialized synaptic formations were observed in only 20.1% of these nodules. The results suggest that bulbospinal descending noradrenergic neuron systems influence the functioning of pelvic muscles principally via the neuronal contacts with dendritic bundles in the spinal cord.
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  • 38
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    Anatomy and embryology 173 (1985), S. 45-52 
    ISSN: 1432-0568
    Keywords: Substance P ; Hippocampus ; Entorhinal area ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of substance P (SP) immunoreactive nerve cell bodies and preterminal processes was studied in the rat brain by using several anti-SP-antibodies in combination with immunohistochemical techniques. In normal rats and in rats pretreated with colchicine, SP immunoreactive preterminal processes were found in the hippocampal region, but SP positive cellbodies could be detected only after colchicine pretreatment. Medium-sized to large, multipolar cells immunoreactive for SP were found in stratum oriens of the hippocampal subfield CA3 and in the hilus of the area dentata. Medium-sized to small, round or fusiform cells were detected in the pyramidal layer of the ventral subiculum and in layers III–VI of the ventral entorhinal area. The SP stained preterminal processes were of two types. Numerous fine, varicose axons were stained in different parts of Ammon's horn, while in the retrohippocampal structures, the SP immunoreactivity was present in small distinctly stained puncta. These frequently formed pericellular arrangements around unstained cells, indicative of axosomatic contacts between SP terminals and cells in the hipocampus. In Ammon's horn, the densest SP innervation was found in strata oriens, radiatum and moleculare of subfields CA3a and CA2. Scattered fibers were also present in the stratum oriens of CA3a-c and in the hilus, in particular at ventral levels. In retrohippocampal structures, the SP innervation predominated in the deep pyramidal layer of the subiculum, the second layer of the presubiculum and in layers VI and IV of the medial and lateral entorhinal area. Many of these terminals may arise from local interneurons as well as from sources outside the hippocampal region. Taken together, these studies demonstrate a far more extensive innervation by SP, or a closely related peptide, of the rat hippocampal region than was previously recognized. This suggests that SP may play an important role in neurotransmission within the hippocampal region.
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  • 39
    ISSN: 1432-0533
    Keywords: Rat ; ENU ; Brain tumor ; Anti-Leu 7 ; GFAP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To clarify the chronologic changes in the cellular morphology of ENU-induced rat brain tumors, microtumors in the early stage were examined ummunohistochemically in comparison with macrotumors in the advanced stage. The tumor cells composing microtumors were negative for glial fibrillary acidic protein (GFAP), a specific marker of astrocylic cells, and Leu 7, a marker of oligodendrocytes, while cells of macrotumors were positive for either GFAP or Leu 7, showing characteristics of mature glial cells. The results suggested that the small round cells in the early devolopmental stage, generally thought to resemble mature oligodendrocytes, are not differentiated oligodendrocytes or astrocytes.
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  • 40
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    Acta neuropathologica 67 (1985), S. 170-173 
    ISSN: 1432-0533
    Keywords: Ethanol ; Rat ; Parietal cortex ; Nuclear inclusions ; Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Wistar rats with an average initial body weight of 180 g received a 15% (v/v) ethanol-water solution over a period of 6 months. Neurons of the parietal cortex (area 3) showed a significant increase of nuclear inclusions which consisted of parallel filaments and tubular systems. Furthermore, we observed and augmentation of lipid droplets, nemetosomes, and straight filaments. The latter could not be identified in control animals. It is discussed whether the occurrence of these structures might be enhanced by an altered cellular metabolic activity during the chronic ethanol administration.
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  • 41
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    Acta neuropathologica 67 (1985), S. 37-50 
    ISSN: 1432-0533
    Keywords: Hypoglycemia ; Cerebral damage ; Dark neurons ; Neuronal necrosis ; Caudate ; Putamen ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The caudate nucleus and putamen belong to the selectively vulnerable brain regions which incur neuronal damage in clinical and experimental settings of both hypoglycemia and ischemia. We have previously documented the density and distribution of the hypoglycemic damage in rat caudoputamen, but the evolution of the injury, i.e., the sequence of structural changes, has not been assessed. Therefore, in the present study we analyze the light and electron microscopic alterations in the caudoputamen of rats exposed to standardized, pure insults of severe hypoglycemia with isoelectric EEG for 10–60 min, or in rats which, following insults of 30 or 60 min, were allowed to recover for periods from 5 min to 6 months. The hypoglycemic insult produced severe nerve cell injury in the dorsolateral caudoputamen. Immediately after the insult abnormal light neurons with clearing of the peripheral cytoplasm were present. These cells disappeared early in the receovery period, as they do in the cerebral cortex. Dark neurons were also present, but unlike those in the cerebral cortex they did not appear until recovery was instituted. Their number increased for a couple of hours and they became acidophilic within 4–6 h. At this stage, electron microscopy revealed severe clumping of the nuclear chromatin and cytoplasm as well as incipient fragmentation of cell membranes, all these changes indicating an irreversible injury. Within 24 h flocculent densities appeared in the mitochondria and by day 2–3 of recovery the great majority of the medium-sized neurons had undergone karyorrhexis and cytorrhexis, their remnants being subsequently removed by macrophages. After some weeks only large and a few medium-sized neurons remained amidst reactive astrocytes and numerous macrophages. The delay in the appearance of dark, lethally injured medium-sized neurons until the recovery was instituted suggests an effect that does not become apparent until the substrate supply and energy production are restored. Furthermore, it pointt out again the selectivity of the hypoglycemic nerve cell injury with respect to the type (metabolic characteristics?) and topographic location of the neurons.
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  • 42
    ISSN: 1432-0533
    Keywords: Lead ; Rat ; Brain ; Blood-brain barrier ; Specific gravity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies on the toxic effects of lead on the brains of young animals have shown damage to the blood-brain barrier (BBB) which in severe forms appears as hemorrhagic encephalopathy. In those studies the doses of lead have been of such magnitude that lead-induced anorexia resulting in growth retardation has contributed to the extent of the injury (Sundström et al. 1984). The growth retardation can be prevented by using low lead doses (Sundström et al. 1983). Consequently, we have examined to which extent the BBB is injured in suckling rats with low dose lead encephalopathy. This was done by a) testing the permeability of the BBB to plasma proteins and b) assessing the possible occurrence of vasogenic edema by measuring the specific gravity of brain tissue. Low dose lead encephalopathy was induced by daily i.p. injections of lead nitrate 10 mg/kg body weight (b.wt.) for the first 15 days. The lead contents of the blood and homogenates of the cerebrum and cerebellum were assayed by atomic absorption spectrophotometry. The brains were examined at 15, 20, or 30 days of age. When Evans blue-albumin (EBA) was injected i.v. 2 h before killing, most 15-day-old rats exposed to lead displayed a bluish discoloration in their cerebellum. Microscopically, red fluorescence of EBA was seen in the blue-stained regions. Immunohistochemically, extravasation of albumin, fibrinogen, and fibronectin was demonstrated as positive staining in the cerebellar cortex, with diffuse spread to the white matter of the corresponding folium. Neither lead-exposed rats aged 20 or 30 days nor any non-exposed rats revealed macroscopic or microscopic leakage of plasma proteins in the brain parenchyma. The specific gravity of the cerebral and cerebellar cortices and the hippocampus of control and lead-exposed rats aged 15 and 20 days was determined using density gradients of Percoll. No increment in the water content was encountered. Rather, the specific gravity of cerebellum of lead-treated rats aged 15 days was slightly higher than that of the controls, though statistical significance for this difference was reached only when nonparametric tests were applied. Our results indicate that low dose lead encephalopathy results in a breakdown of the BBB to plasma proteins without marked vasogenic brain edema. The hypothesis is advanced that the leakage of plasma results in rapid normalization of the tissue water content, whereas proteins remain longer in the parenchyma.
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  • 43
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    Anatomy and embryology 171 (1985), S. 285-296 
    ISSN: 1432-0568
    Keywords: Congenital aganglionosis ; Myenteric plexus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The entire bowel of a mutant strain of rats, the congenital aganglionosis rat (spotting lethal), was investigated using the acetylcholinesterase reaction and immunohistochemical staining for tyrosine hydroxylase and substance P in whole-mount preparations. The histology of the bowel of mutant rats was also studied by light- and electron microscopy. In all examined mutant rats, a constricted region of intestine followed a dilated region of the bowel. In 29 cases constricted segments extended from rectum to distal ileum; in 3 cases from rectum to middle colon. In controls the myenteric plexus appeared as a mesh-work consisting of ganglion strands and internodal strands, showing a rather regular ladder-like pattern from duodenum to rectum. The myenteric plexus of mutants was very different from that of controls, showing conspicuous regional differences. Even in the duodenum, where there was no macroscopical disorder, the plexus showed an irregular pattern, the meshes varying greatly in size and shape. Ganglion strands were shorter than those in controls. The plexus in the dilated segment gradually decreased in density, finally disappearing above the proximal terminal of the constricted segment. In some areas, below this transition, i.e., the anal portion of the constricted segment in 29 cases (long constricted segment type only), there were neither ganglion cells nor nerve fibers except for scarcely distributed tyrosine hydroxylase-immunoreactive nerve fibers. In the distal part of the upper colon some fine nerve bundles, gradually increased in number and mixed with thicker nerve bundles in the lower portion of the colon. Finally, at the level of the rectum, nerve bundles of various sizes interlaced irregularly with one another to form a network. However, this network was free from ganglion cells.
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  • 44
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    Anatomy and embryology 172 (1985), S. 195-204 
    ISSN: 1432-0568
    Keywords: Pyramidal tract ; Growth cones ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An electron microscopic study has been made of the tip of the growing pyramidal tract in the rat. This part of the developing bundle, designated as the growthzone, has been examined at the levels of the medulla oblongata and the third spinal segment at embryonic day 20 and on the day of birth, respectively. The tip of the pyramidal tract contains, apart from axons, numerous larger profiles. An analysis of serial sections revealed that these represent either growth cones or preterminal periodic varicosities. In the growth cones of the corticospinal axons three zones can be distinguished: a proximal “tubular”, an intermediate ”vesicular-reticular” and a distal “fine-granular” zone. As distinct from the classical descriptions the corticospinal growth cones end in a single or, less frequently, in two more or less parallel filopodia. None of the growth cones analyzed in this study showed multiple filopodia radiating from the terminal expansion as observed at the end of growing axons in tissue cultures and in developing spinal fibre tracts of nonmammalian vertebrates. As regards the varicosities, most of these structures are characterized by a light cytoplasmic density. Others, however, contain a denser cytoplasm, closely resembling that of the vesiculo-reticular part of growth cones.
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  • 45
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    Anatomy and embryology 172 (1985), S. 39-48 
    ISSN: 1432-0568
    Keywords: Lateral geniculate nucleus ; Relay cells ; Development ; Synaptogenesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphology and synaptic input of four geniculo-cortical relay neurons of albino rats of postnatal day (PD) 7 has been studied with light and electron microscopy, utilizing the combined Golgi-EM technique. Although the nerve cells investigated did show a characteristic relay-cell appearance of the adult, certain dendritic structures exhibited immature character. These were the dendritic swellings, or “growth buds” occurring throughout the whole length of the dendrites, but particularly along the segments and at bifurcations of thin distal dendritic portions. These dendritic thickenings together with the transient spine-like hairy processes were seen to receive many synaptic endings of various developmental stages. The majority of synaptic junctions both on the dendritic swellings and on dendritic shafts were of the asymmetric type. Contrary to our expectation, no proximo-distal gradient could be demonstrated in the maturation of axodendritic synapses, at least not during the first synaptogenetic period, i.e., at PD 7. Also, all axosomatic synapses in the PD7 rat LGNd were asymmetric, indicating that the replacement of asymmetric synapses by symmetric ones (characteristic for the adult stage) occurs only after the first synaptogenetic period. The rarity of Gray II type, symmetric contacts during the early synaptogenesis (i.e., at PD 7) explains the absence of triadic, or serial synapses which will develop only later, during the second synaptogenetic period.
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  • 46
    ISSN: 1432-0568
    Keywords: Serotonin receptors ; Cerebral cortex ; Ontogenesis ; Rat ; Quantitative autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of serotonin (5-HT1) receptors in various cortical regions of the rat brain has been examined during ontogenesis by quantitative autoradiography. An increase in binding site density between the first postnatal day and adult age was observed and could be approximated by a sigmoid shaped (logistic) growth curve. A marked heterochrony in the increase of binding site density is found in the 13 analyzed cortical regions. Binding sites develop earlier in neocortex than in allocortical areas. Fifty pereent of the binding site density of adult age is reached in the motor cortex at the 9th postnatal day, followed by the primary somatosensory cortex one day later, by the medial prefrontal cortex on the 12th day, by the fascia dentata on the 14th day and by the CA1-region on the 20th day. A detailed analysis of the frontal, medial prefrontal and hippocampal regions also shows a heterochrony within these regions. Adult values of binding site densities are also reached at different ages in the various cortical regions. The highest receptor densities were observed in the dorsal subiculum, the lowest in the primary somatosensory cortex.
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  • 47
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    Annals of hematology 50 (1985), S. 109-112 
    ISSN: 1432-0584
    Keywords: Sudanophilia ; Rat ; Lymphocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A significant proportion of large lymphocytes in laboratory rats is stained with Sudan black B. The increase in the counts of sudanophilic blood lymphocytes over control values indicated reliablely the recovery of lymphocytic function even when total lymphocyte, small or large lymphocyte counts were normal or reduced.
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  • 48
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    Acta neuropathologica 67 (1985), S. 13-24 
    ISSN: 1432-0533
    Keywords: Hypoglycemia ; Cerebral cortex ; Nerve cell injury ; Dark neurons ; Acidophilic neurons ; Mitochondria ; Golgi apparatus ; Cell necrosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the course of a study on the pathogenesis of neuronal necrosis in severe hypoglycemia, the morphological characteristics reflecting reversible and irreversible neuronal lesions were examined as a function of time following normalization of blood glucose. To that end, closely spaced time intervals were studied in the rat cerebral cortex before, during, and up to 1 year after standardized pure hypoglycemic insults of 30 and 60 min of cerebral isoelectricity. Both the superficial and deep layers of the cerebral cortex showed dark and light neurons during and several hours after the insult. By electron microscopy (EM) the dark neurons were characterized by marked condensation of both karyoplasma and cytoplasm, with discernible, tightly packed cytoplasmic organelles. The light neurons displayed clustering of normal organelles around the nucleus with clearing of the peripheral cytoplasm. Some cells, both dark neurons and neurons of normal electron density, contained swollen mitochondrial with fractured cristae. Light neurons disappeared from the cerebral cortex by 4 h of recovery. Some dark neurons in the superficial cortex and almost all in the deep cortex evolved through transitional forms into normal neurons by 6 h recovery. Another portion of the dark neurons in the superficial cortex became acidophilic between 4 and 12 h, and by EM they demonstrated karyorrhexis with stippled electron-dense chromatin. The plasma membrane was disrupted, the cytoplasm was composed of amorphous granular debris, and the mitochondria contained flocculent densities. These definitive indices of irreversible neuronal damage were seen as early as 4–8 h recovery. Subsequently, the acidophilic neurons were removed from the tissue, and gliosis ensued. Thus, even markedly hyperchromatic “dark” neurons are compatible with survival of the cell, as are neurons with conspicuous mitochondrial swelling. Definite nerve cell death is verified as the appearance of acidophilic neurons at which stage extensive damage to mitochondria is already seen in the form of flocculent densities, and cell membranes are ruptured. Our previous results have shown that hypoglycemic neocortical damage affects the superficial laminae, chiefly layer 2. The present results demonstrate that, following the primary insult, this damage evolves relatively rapidly within the first 4–12 h. We have obtained no evidence that additional necrotic neurons are recruited after longer recovery periods.
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  • 49
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    Development genes and evolution 194 (1985), S. 429-432 
    ISSN: 1432-041X
    Keywords: Tail bud ; Tail gut ; Gut ; Organogenesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The formation of the tail portion of the primitive gut was investigated by light and electron microscopy in 10- and 11-day rat embryos. The observations permit the conclusion that the tail gut does not form as a posterior extension of the hindgut but originates from the tail bud mesenchyme by mechanism analogous to the secondary neurulation. It includes cell condensation, aquisition of apicobasal polarity and the radial, rosette-like arrangement around a central cavity. These cells bear the cytological characteristics of both the absorptive epithelial cells and the mesenchymal cells at their apical (adluminal) and abluminal ends respectively.
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  • 50
    ISSN: 1420-9071
    Keywords: Rat ; alloxan diabetes ; intestinal villus ; alkaline phosphatase ; sucrase ; epithelial cells ; villus-crypt axis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The sucrase activity in enterocytes isolated from the villus crypt axis was found to increase in all regions of the villus from day 2 after induction of diabetes, and the increase continued until day 4. In contrast, alkaline phosphatase activity increased mainly in the apical one-third of the villus-crypt column, and the increase occurred abruptly on day 4 with increase in food intake.
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  • 51
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    Acta neuropathologica 65 (1985), S. 209-216 
    ISSN: 1432-0533
    Keywords: Hydrocephalus ; β,β′-Iminodipropionitrile ; Rat ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary β,β′-Iminodipropionitrile (IDPN), a neurotoxic compound known to induce swellings in the proximal internodes of sensory and motor axons in several parts of the central nervous system (CNS), was also found to cause hydrocephalus in rats and guinea pigs. In both species, ventricular dilatation was observed within 1 week following a single i.p. injection of IDPN. While in rats the severity of hydrocephalus correlated with dose and duration of IDPN exposure, in guinea pigs studies with high doses yielded inconclusive results, and no significant temporal correlation was noted. Parallel investigations with another peurotoxic agent, acrylamide, in rats, and with IDPN in cats failed to demonstrate any change in size and shape of the cerebrospinal fluid (CSF) pathways. No signs of spontaneously occurring hydrocephalus were found in control animals. In both rats and guinea pigs intoxicated with IDPN, macroscopic and microscopic findings were consistent with the diagnosis of communicating hydrocephalus. Treatment of hydrocephalic rats with acetazolamide (500 mg/kg) markedly attenuated ventricular distention, suggesting that an overproduction of CSF by the choroid plexus is responsible for the communicating hydrocephalus following IDPN intoxication.
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  • 52
    ISSN: 1432-0428
    Keywords: Rat ; hepatic pyruvate dehydrogenase complex ; blood lactate ; glucose ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary At birth, hepatic ‘active’ and ‘dichloracetate-activated’ pyruvate dehydrogenase complex activities in the newborn of normal, mildly diabetic, and severely diabetic rats were similar. The ‘active’ and ‘dichloracetate-activated’ pyruvate dehydrogenase complex activities increased significantly during the first 2 and 6 postnatal h, respectively in the three groups of neonates (p〈0.05). The greatest increase in both ‘active’ and ‘dichloroacetate-activated’ pyruvate dehydrogenase complex activity was observed in the neonates of mildly diabetic rats. Administration of glucose or insulin at birth to the newborn of normal rats caused a significant increase in the percentage of ‘active’ pyruvate dehydrogenase complex activity within 1 h (p〈0.01). Similar treatment caused no significant increases in the newborn of severely diabetic rats. The transient increases in ‘active’ pyruvate dehydrogenase complex activity in the neonates of normal and diabetic rats were consistent with rapid disappearance of blood lactate during the first hours of postnatal life.
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  • 53
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    Cellular and molecular life sciences 41 (1985), S. 273-275 
    ISSN: 1420-9071
    Keywords: Rat ; embryo ; embryo ; rat ; β-hydroxybutyrate ; diabetes ; maternal ; fetal malformation ; malformation ; fetal ; ketone bodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In order to investigate further the relationship between maternal diabetes and fetal malformation, rat embryos were grown in vitro in the presence of β-hydroxybutyrate, one of the ketone bodies produced by diabetics. At 10 mM, β-hydroxybutyrate produced minor abnormalities and at 20 mM it produced major abnormalities in rat embryos.
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  • 54
    ISSN: 1432-1106
    Keywords: Granule cells ; Dendrites ; Golgi stain ; Dentate gyrus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The dendritic morphology of Golgistained hippocampal dentate granule cells was evaluated by measuring the amount and location of dendrite, and the number of length of dendritic branches. Granule cells with somata in the superficial third of the granule cell layer had substantially more dendritic material than those with somata in the deep portions of the cell layer; this difference occurred throughout the extent of the molecular layer. Superficial cells also had different dendritic branching patterns and wider dendritic fields than did cells located in the deeper two-thirds of the granule cell layer. These results indicate that the position of neurons within the cell layer should be taken into account when quantifying the dendritic fields of dentate granule cells.
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  • 55
    ISSN: 1432-1106
    Keywords: GABAergic neurons ; Accessory optic nuclei ; Pretectal nuclei ; Gerbil ; Rat ; Visual system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The enzyme glutamic acid decarboxylase (GAD) has been localized in sections of rodent brains (gerbil, rat) using conventional immunocytochemical techniques. Our findings demonstrate that large numbers of GAD-positive neurons and axon terminals (puncta) are present in the visual relay nuclei of the pretectum and the accessory optic system. The areas of highest density of these neurons are in the nucleus of the optic tract (NOT) of the pretectum, the dorsal and lateral terminal accessory optic nuclei (DTN, LTN), the ventral and dorsal subdivisions of the medial terminal accessory optic nucleus (MTNv, MTNd), and the interstitial nucleus of the posterior fibers of the superior fasciculus (inSFp). The findings indicate that 27% of the NOT neurons are GAD-positive and that these neurons are distributed over all of the NOT except the most superficial portion of the NOT caudally. The GAD-positive neurons of the NOT are statistically smaller (65.9 μm2) than the total population of neurons of the NOT (84.3 [j,m2) but are otherwise indistinguishable in shape from the total neuron population. The other visual relay nuclei that have been analyzed (DTN, LTN, MTNv, MTNd, inSFp) are similar in that from 21% to 31% of their neurons are GAD-positive; these neurons are smaller in diameter and are more spherical than the total populations of neurons. The data further show that a large proportion of the neurons in these visual relay nuclei are contacted by GAD-positive axon terminals. It is estimated that approximately one-half of the neurons of the NOT and the terminal accessory optic nuclei receive a strong GABAergic input and have been called “GAD-recipient neurons”. Further, the morphology of the GAD-positive neurons combined with their similar distribution to the GAD-recipient neurons suggest that many of these neurons are acting as GABAergic, local circuit neurons. On the other hand, the large number of GAD-positive neurons in the NOT and MTN (20–30%) in relation to estimates of projection neurons (75%) presents the possibility that some may in fact be projection neurons. The overall findings provide morphological evidence which supports the general conclusion that GABAergic neurons play a significant role in modulating the output of the visually related NOT and terminal accessory optic nuclei.
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  • 56
    ISSN: 1432-1106
    Keywords: Hippocampus lesion ; Partial reinforcement ; Delay of reinforcement ; Inter-trial interval ; Inter-event interval ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two experimental procedures were employed to establish the reason why hippocampal lesions apparently block the development of tolerance for aversive events in partial reinforcement experiments, but do not do so in partial punishment experiments. Rats were trained to run in a straight alley following hippocampal lesions (HC), cortical control lesions (CC) or sham operations (SO), and resistance to extinction was assessed following differing acquisition conditions. In Experiment 1 a 4–8 min inter-trial interval (ITI) was used. Either every acquisition trial was rewarded immediately (Continuous Reinforcement, CR), or only a randomly selected half of the trials were immediately rewarded, the reward being delayed for thirty seconds on the other trials (Partial Delay, PD). This delay procedure produced increased resistance to extinction in rats in all lesion groups. In Experiment 2 the ITI was reduced to a few seconds, and rats were trained either on a CR schedule, or on a schedule in which only half the trials were rewarded (Partial Reinforcement, PR). This form of partial reinforcement procedure also produced increased resistance to extinction in rats in all lesion groups. It thus appears that hippocampal lesions only prevent the development of resistance to aversive events when the interval between aversive and subsequent appetitive events exceeds some minimum value.
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  • 57
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    Experimental brain research 57 (1985), S. 537-546 
    ISSN: 1432-1106
    Keywords: Substance P ; Facial nucleus ; Medullary reticular formation ; Axo-dendritic contacts ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution, origin and fine structure of substance P-like immunoreactive (SPI) nerve terminals in the facial nucleus of the rat were investigated by means of immunocytochemistry. SPI-terminals were concentrated in the intermediate and dorsal subnuclei of the facial nucleus. Hemi-transection of the brainstem just rostral to the facial nucleus or at the most caudal level of the medulla oblongata did not cause any change of SPI-terminals in the facial nucleus. Electrical destruction of the various parts of the medulla oblongata clearly demonstrated that SPI-terminals in the intermediate subnucleus were supplied contralaterally from the SPI-neurons in the dorsomedial part of the medullary reticular formation. Most of the SPI-terminals (85%) in the intermediate subnucleus of the facial nucleus were observed to make asymmetric synaptic contacts with large dendrites (mean diameter; 1.26 μm). It was supposed that the contact sites are located on proximal parts of the dendrite. A few SPI-terminals (6%) formed axo-somatic contacts with large perikarya filled with numerous cytoplasmic organelles.
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  • 58
    ISSN: 1432-1106
    Keywords: Rat ; Luminance detector ; Darkness detector ; Pupil ; Sympathectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to identify the pretectal nucleus which contains pupillomotor cells in the rat, cells were sought which were sensitive to changes in luminance level at the eye. Two types were found: Luminance detectors which showed a graded increase in firing with increase in luminance, and darkness detectors which showed a graded increase in firing rate with graded dimming of luminance intensity. All luminance detectors were located in the olivary pretectal nucleus, whereas darkness detectors were located in the posterior pretectal nucleus. Consensual pupil responses were recorded in conscious normal and sympathectomised rats using an infra-red sensitive T.V. pupillometer. Pupil diameter varied 2mm in an approximately linear fashion over six log units range in luminance intensity. Sympathectomy produced a general constriction of the pupil, but the overall response to light was unaffected. The changes in pupil size occurred over the same range of luminance that the firing rates of both luminance and darkness detectors changed. The olivary pretectal nucleus may therefore be involved in pupilloconstruction in the light, and the posterior pretectal nucleus, with pupillodilation in the dark.
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  • 59
    ISSN: 1432-1106
    Keywords: Rat ; Nucleus reticularis gigantocellularis ; Reticulospinal ; Laminae I, II and IX
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have used the autoradiographic method to study the organization of spinal projections from the gigantocellular reticular nucleus in the rat. Of particular note was the evidence obtained for projections to laminae I, II and IX. Reticular projections to laminae I and II arise more rostrally in Gi than those to lamina IX. Projections to laminae III–VIII and X as well as to autonomic nuclei have also been documented. Our results suggest that the gigantocellular reticular nucleus of the rat can be subdivided on connectional grounds.
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  • 60
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    Experimental brain research 59 (1985), S. 559-569 
    ISSN: 1432-1106
    Keywords: Rat ; Superior colliculus ; Visual neglect ; Field defect ; Striate cortex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous work has been shown that rats with lesions of the superior colliculus fail to respond to distracting visual stimuli presented in the peripheral field while the animals are running towards a central stimulus. To assess how far this peripheral neglect is due to an attentional deficit, rats were trained before operation to obtain reward by running towards either peripheral or central lights that were presented when the animals' heads were stationary in a known position. Response to stimuli presented 120 deg from the midline was severely impaired after removal of the superior colliculus: the animals behaved as if they had difficulty in detecting the onset of the light. In contrast, response to stimuli 40 deg from midline was unaffected. Control lesions of striate cortex did not significantly impair performance at any position. The finding that collicular animals were impaired at responding to stimuli in the far periphery, that were not irrelevant distractors but instead predicted reward, suggests that one component of the visual neglect produced by damage to the superior colliculus in rats may be a sensory deficit in the far peripheral field. In addition, comparison with previous results indicates that training to attend to visual stimuli in more central regions does improve performance, as would be expected if the deficit were an attentional one. It is therefore argued that collicular neglect in rats should be regarded as a multicomponent impairment.
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  • 61
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    Experimental brain research 57 (1985), S. 256-263 
    ISSN: 1432-1106
    Keywords: Swallowing ; Medullary swallowing neurons ; Nucleus of the solitary tract ; Unit activity (extracellular microelectrodes) ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present study was to identify the central structures involved in the organization of the swallowing reflex in the rat. Using concentric bipolar electrodes, the medulla and pons were systematically explored in order to determine which central areas responded to stimulation by inducing swallowing. These areas, which were located in the dorsal medulla oblongata, were the solitary tract, the nucleus of the solitary tract (NST) and the adjacent reticular formation. Stimulation of the ventral ponto-medullary regions was ineffective with regard to the initiation of the swallowing reflex. The activity of medullary swallowing neurons was recorded using extracellular microelectrodes. These swallowing neurons responded with a burst of spikes (swallowing activity) which was closely linked to the swallowing reflex elicited by stimulation of the superior laryngeal nerve (SLN). Under SLN stimulation, the activity of some of the swallowing neurons furthermore showed an initial response consisting of 1 or 2 spikes after a brief latency. According to their location and the latency of their initial response, swallowing neurons were divided into two groups. Group I neurons were located in a dorsal area of the medulla oblongata corresponding to the NST and the adjacent reticular formation. All these neurons exhibited an initial response with a very short latency (1 to 4 ms), the swallowing activity of most of these neurons started before the onset of the swallowing motor sequence. Group II neurons were located either in a ventral area corresponding to the nucleus ambiguus and the surrounding reticular formation or in a dorsal and medial area corresponding to the hypoglossal nucleus and its vicinity. Some of these neurons also exhibited an initial response to SLN stimulation, but with a longer latency (7–12 ms). Motor paralysis of the animal (performed by curare injection) did not affect the swallowing activity of the neurons belonging to either group. Thus, the swallowing activity of the medullary neurons studied was a truly central activity. It is concluded that the swallowing neurons studied belonged to the medullary swallowing center; the group II neurons were motoneurons and interneurons forming the efferent stage of the swallowing center, and the group I neurons were the interneurons which largely belong to the center which programs the swallowing motor sequence.
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  • 62
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    Experimental brain research 57 (1985), S. 471-479 
    ISSN: 1432-1106
    Keywords: Rat ; Lateral geniculate nucleus ; Thalamic reticular nucleus ; Bursts ; Inhibition ; Receptive fields
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two-shock inhibition, a feature of 98 of 100 P cells recorded in the dorsal lateral geniculate nucleus of the normal rat, was not observed in 91 of 140 geniculate cells after an electrolytic lesion had been made in the adjacent visually responsive thalamic reticular nucleus. Nine geniculate cells recorded both before and after a reticular lesion had their initial inhibition abolished or substantially reduced after the lesion. The reticular lesion eliminated the bursts of spikes which normally terminate periods of inhibition following electrical or photic stimulation but caused no other changes in receptive field organization of geniculate cells. We conclude that the visually responsive region of the thalamic reticular nucleus in the rat is responsible for the profound two-shock inhibition and for the post-inhibitory bursts which are normal properties of relay cells of the dorsal lateral geniculate nucleus.
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  • 63
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    Experimental brain research 58 (1985), S. 183-189 
    ISSN: 1432-1106
    Keywords: Olivocerebellar projection ; Axonal branching ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Axonal branching in the olivocerebellar projection was investigated using the retrograde fluorescent double-labelling method. Combinations of true blue and diamidino yellow injections (50 nl) were made in the cerebellar cortex of anaesthetized rats to investigate branching within single longitudinal zones and branching between such zones. The topographical arrangement of the projection was similar to that previously described, but additionally it was found that lateral parts of the inferior olive project more rostrally within a longitudinal zone and medial parts project more caudally in the same zone. Double-labelled olivary neurones, with axons branching rostrally and caudally within a single zone, were found to lie in an intermediate position between the two groups of single-labelled neurones. No such double-labelled neurones occurred when branching between zones was investigated. The correlation between these anatomical findings and earlier physiological work is discussed.
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  • 64
    ISSN: 1432-1106
    Keywords: Antidromic activation ; Latency variation ; Axonal excitability ; Paraventricular nucleus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Magnocellular neurosecretory cells were antidromically identified in the hypothalamic paraventricular nucleus (PVN) of urethane-anesthetized, ovariectomized female rats following electrical stimulation of the neurohypophysis. Seventy-one cells with a tonic pattern of spontaneous discharge were distinguished and used to examine the relationships between the measures of antidromic spike latency, activation threshold and discharge rate. The discharge rate was artificially modulated by either microiontophoresis of glutamate or antidromic stimulation of the neurohypophysis. In all the PVN cells with tonic activity, the latency lengthened and the threshold increased as a function of the discharge rate. Activation of individual cells by microiontophoresis of glutamate was effective, as was simultaneous activation of many PVN cells by antidromic stimulus. Similar relationships between the discharge rate and the parameters of antidromic activation were seen in 3 cells, when their rates varied spontaneously over a wide range without manipulation. These data suggest that the excitability of axons of presumed oxytocinergic cells in the PVN-neurohypophyseal system are influenced by their prior activity, probably through metabolic changes in individual axons.
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    Experimental brain research 60 (1985), S. 318-322 
    ISSN: 1432-1106
    Keywords: Gustation ; Taste ; Electric taste ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cathodal OFF response in electric taste, the production of a taste sensation at the break of a microampere cathodal current passed through the tongue, was studied electrophysiologically in the rat chorda tympani nerve. Previous work in electric taste has centered on ON responses to both anodal and cathodal currents. The cathodal OFF response, like ON responses, increased with increasing current intensity until a saturated response level was achieved. Unlike previously reported ON responses, the OFF response did not show a sensitivity to the ionic composition of the fluid bathing the tongue making this the first electrophysiological report of ion insensitivity in electric taste. The cathodal OFF response was sensitive to the duration of the current pulse preceding it. Longer pulses produced larger OFF responses, until with very long pulses (seconds) a saturated response level was achieved. The half maximal response occurred at 12.5 ms. These results have been interpreted to mean that the cathodal OFF response has an origin other than the microvillus membrane, the site most often implied for ON responses, due largely to its ion insensitivity. A probable location may reside with ion channels transversing the basal membrane which are transiently excited at the break of the current resulting in excitation at the receptor-afferent synapse.
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  • 66
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    Experimental brain research 60 (1985), S. 501-508 
    ISSN: 1432-1106
    Keywords: Medial terminal accessory optic nucleus ; Rat ; Rabbit and cat ; Neuron morphology ; Dendritic architecture ; Golgi impregnation methods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The neurons of the medial terminal nucleus (MTN) of the accessory optic system (AOS) have been studied in the rat, rabbit and cat in Golgi-Cox and Golgi-Kopsch impregnated brain sections. The present anatomical findings permit a division of the MTN of these species into dorsal and ventral components (MTNd, MTNv), in agreement with other investigations. The MTNd contains predominantly linear-bipolar and linear-multipolar shaped neurons with cell bodies that measure in the range of 25–50 μm. These neurons have 2 to 4 primary dendrites which, along with their smaller dendritic branches, are oriented in the plane of the long axis of the MTN (i.e. from ventromedial to dorsolateral). These linear-bipolar and linear-multipolar cells represent 70–80% of the neurons of the MTNd as seen in the Golgi impregnated sections. The remaining 20–30% of the MTNd neurons are nearly all multipolar in shape with somata measuring in the range of 15–25 μm. An occasional multipolar neuron is larger, has a soma that measures around 30–60 μm and has dendrites which extend outward from the cell body to cover large areas of the MTNd. There was considerable extension of the dendrites of MTNd neurons into the MTNv; however, the dendrites of MTNd neurons were not observed extending into the adjacent substantia nigra (SN) or ventral tegmental area (VTA) of Tsai (1925). Conversely, the dendrites of neurons in the neighboring SN and VTA course along the borders of the MTN but only occasionally extend into the MTN. The neuron population of the MTNv consists almost entirely of small-multipolar shaped cells with somata measuring from 15–25 μm and dendritic trees resembling those described for multipolar cells of the MTNd. A small number of neurons of the ventral division are medium-multipolar in shape with cell bodies that measure approximately 30–60 μm. Typically, these cells have several dendrites which extend ventrally within the MTNv and one or more dendrites that extend either across the MTNv or dorsally into the MTNd. Only a few linear-bipolar and linear-multipolar neurons were observed in the MTNv. The present findings are discussed in relation to anatomical, physiological, and histochemical studies on the MTN.
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  • 67
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    Experimental brain research 60 (1985), S. 564-575 
    ISSN: 1432-1106
    Keywords: Dorsal lateral geniculate nucleus ; Lateroposterior thalamic nucleus ; Superior colliculus ; Microphthalmia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tecto-thalamic projections in the hereditary bilaterally microphthalmic rat were studied by means of WGA-HRP injection into the dorsal lateral geniculate nucleus (LGNd) and the lateroposterior thalamic nucleus (LP). Histological study in the mutant rats showed that whereas LGNd and superficial layers of the superior colliculus (SC) suffered from a remarkable reduction in size, LP had no histological changes as compared to the normal animals. Unilateral injection of the tracer into the microphthalmic LGNd showed that WGA-HRP positive neurons were present mostly in the ipsilateral str. griseum superficiale (SGS) of the SC. However, the number of labeled SGS neurons of the microphthalmic animals was about 3% of the normal. Although cell bodies of the normal tecto-LGNd neurons in the SGS were spindle-form in shape and issued one or two proximal dendrites from each pole, the microphthalmic tecto-LGNd neurons showed an irregular contour and their dendrites were not so intensively labeled. Unilateral injections of WGA-HRP into the LP revealed that the tecto-LP neurons were mainly distributed in the ipsilateral str. opticum of the colliculus. (SO) in both normal and microphthalmic animals. However, the number of labeled SO cells in the microphthalmic rat was about one-half of the normal. Furthermore, the size of labeled tecto-LP neurons was smaller than that of the normal ones, and they showed irregular round to oval cell bodies with equivocally labeled dendrites, in contrast to the normal tecto-LP neurons with polygonal cell bodies extending three or more dendrites in a radial fashion. These results indicate that there exist the tecto-LGNd and -LP projection neurons in the microphthalmic rat and that their laminally segregated projection is fundamentally preserved. However, the number of the tecto-thalamic projection neurons, especially of the tecto-LGNd cells, was markedly diminished in the mutant tectum compared to normals.
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  • 68
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    Naunyn-Schmiedeberg's archives of pharmacology 328 (1985), S. 354-357 
    ISSN: 1432-1912
    Keywords: Autoradiography ; β-Adrenoceptor subtypes ; Kidney ; Rat ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present autoradiographical study examines the distribution of the two β-adrenoceptor subtypes in sections of rat and guinea-pig kidney. The radioligand [125Iodo]-(-)-cyanopindolol was used for the labelling of β-adrenoceptors and the selective β-adrenoceptor blocking agents ICI 89-406 (β1-antagonist) and ICI 118-551 (β2-antagonist) were utilized to differentiate both subclasses unequivocally. β-Adrenoceptors in rat kidney were found to be almost exclusively β1. They were located mainly on glomeruli and to a lesser extent on the straight part of the distal tubules and on the cortical portion of the collecting ducts. Some β2-adrenoceptors were localized around the corticomedullary junction. Grain localization in the autoradiograms was absent in the inner medulla and papilla. Glomeruli and distal tubules of the guinea-pig kidney also possess only β1-adrenoceptors, but, in contrast to the rat, extremely high concentrations of β2-adrenoceptors were associated with the straight part of the proximal tubules in the cortex and possibly with the cortical portion of the collecting duct. Labelling was not detected on the proximal convoluted tubule in either species.
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    Naunyn-Schmiedeberg's archives of pharmacology 331 (1985), S. 225-234 
    ISSN: 1432-1912
    Keywords: γ-Aminobutyric acid (GABA) ; Noradrenaline turnover ; Locus coeruleus ; Impulse flow ; GABA mimetics ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to explore the nature of the facilitatory GABAergic control of cerebral noradrenergic neurons, we have studied the effect of a variety of GABA mimetics (given systemically or injected locally into brain areas containing noradrenergic cell bodies or terminals) on several indices of noradrenaline turnover in the rat brain. Systemic administration of both direct and indirect acting GABA mimetics enhanced; 1) the pargyline induced accumulation of normetanephrine in the hypothalamus; 2) total DOPEG levels in a number of brain regions innervated by noradrenergic neurons; 3) both DOPAC and MOPEG levels in noradrenergic cell body areas (A1, A2 and A6). These effects are probably mediated by GABAA receptors as specific GABAA or mixed GABAA/GABAB agonists but not the GABAB agonist baclofen enhanced noradrenaline turnover. Interruption of noradrenergic impulse flow (by local injection of tetrodotoxin or by hemitransection) blocked the ability of progabide to increase DOPEG concentrations in the hypothalamus and cerebral cortex. Similarly, the coadministration of clonidine with progabide antagonized the progabide-induced increase in hypothalamic total DOPEG levels. Co-administration of yohimbine with progabide provoked an additive effect on hypothalamic DOPEG levels at moderate but not at high doses of yohimbine. Thus, the acceleration of noradrenaline turnover induced by GABA mimetics appears to depend on ongoing activity in noradrenergic neurons and occurs via an increase in neuronal discharges. Local injection of muscimol into the nucleus accumbens or hypothalamus failed to affect DOPEG levels in these structures; similarly, local injection of muscimol into the locus coeruleus failed to modify DOPEG levels in corresponding noradrenergic projection areas. These data indicate that the GABAergic influence is not exerted via GABA receptors located on noradrenergic cell bodies or nerve endings. Furthermore, since systemically administered progabide still increased hypothalamic DOPEG levels after ibotenate-induced destruction of the hypothalamic neuronal cell bodies, a presynaptic modulation of noradrenergic neurons by local GABAergic interneurons is excluded. Chemical desctruction of serotoninergic pathways or enhancement of 5-HT transmission by quipazine failed to alter the ability of progabide to increase cerebral DOPEG levels. Moreover, seopolamine or naloxone also failed to affect the progabide-induced increase in cerebral DOPEG levels. These results exclude the implication of serotoninergic, cholinergic and opioid systems in the mediation of the facilitatory influence of GABA on noradrenergic neurons. It is concluded that the facilitatory GABAergic influence on cerebral noradrenergic transmission is probably indirect and mediated via GABAergic synapses involved in transsynaptic neuronal circuits (the nature of which remains to be defined) regulating noradrenergic cell activity.
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    Psychopharmacology 87 (1985), S. 292-297 
    ISSN: 1432-2072
    Keywords: Brain syndrome ; Cerebral ventricles ; Intraventricular injection ; Rat ; Psychosis ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A new experimental brain syndrome involving localized periventricular damage induced by intracerebroventricular injections of lysophosphatidyl choline has been developed in adult rats. The acute periventricular injury syndrome is characterized by transient weight loss, decreased emotionality, extreme postural indifference (catalepsy), inappropriate aggressive responses, impaired grooming, cerebral ventricular enlargement, and periventricular damage to both cells and fiber sheaths. This syndrome appears to simulate several features of schizophrenia, and it may prove useful in the study of psychotic disorders in man.
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    Psychopharmacology 86 (1985), S. 147-152 
    ISSN: 1432-2072
    Keywords: Benzodizepines ; Indalpine ; Zimelidine ; Serotonergic neurons ; Waiting capacity ; Impulse control ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated whether benzodiazepines reduce the capacity of animals to wait for food reward. Rats trained in a T-maze were allowed to choose between two magnitudes of reward: immediate, but small (two pellets) vs delayed, but large (eight pellets). The rats learned within ten sessions to select (80–100%) the arm leading to the largest reward. Separate groups of rats were then confined for 15, 30 or 60 s in the arm associated with the largest reward before gaining access to the spacially contiguous goal-box. The choice of the other arm was not followed by a period of waiting. Under these conditions, the frequency with which the small-reward arm was chosen increased linearly as a function of the duration of the waiting period. Diazepam (2–4 mg/kg IP) dose-dependently increased the number of times the small-reward arm was chosen during the sessions for which the waiting period was fixed at 15 or 30 s. Nitrazepam (2 mg/kg IP), chlordiazepoxide (16 mg/kg IP) and clobazam (16 mg/kg IP) had similar effects. The action of diazepam was counteracted by simultaneous administration of flumazepil (Ro 15-1788, 8 mg/kg PO). In the absence of confinement, these benzodiazepines, diazepam (4 mg/kg) excepted, did not modify selection of the large-reward arm. Conversely, the serotonin uptake blockers indalpine (2–4 mg/kg IP) and zimelidine (8–16 mg/kg IP) dose-dependently increased preference for the arm leading to the delayed (25 s) but large reward. These results suggest that benzodiazepines, perhaps by increasing impulsivity, render the animals less prone than controls to tolerate delayed access to reward. It is hypothesized that serotonergic neurons play a crucial role in impulse control and in the benzodiazepines-induced shift towards the immediate reward.
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  • 72
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    Psychopharmacology 86 (1985), S. 318-323 
    ISSN: 1432-2072
    Keywords: dl-Amphetamine ; Continuous reinforcement ; Partial reinforcement ; Resistance to extinction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of amphetamine administration on the partial reinforcement extinction effect (PREE) at one trial a day, were examined. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasirandom 50% schedule. All animals were then tested inextinction. dl-Amphetamine 1.5 mg/kg was administered in a 2×2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. The PREE, i.e., increased resistance to extinction exhibited by PRF animals as compared to CRF animals, was obtained in animals that received saline in acquisition, independently of drug treatment in extinction. In contrast, amphetamine administered in acquisition abolished the PREE irrespective of drug treatment in extinction. In addition, amphetamine administered in extinction alone increased resistance to extinction in PRF animals.
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  • 73
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    Psychopharmacology 86 (1985), S. 68-76 
    ISSN: 1432-2072
    Keywords: Maternal aggression ; Female aggression ; Offense ; Defense ; Ethopharmacology ; Fluprazine ; Chlordiazepoxide ; Serenics ; Benzodiazepines ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although maternal agression in rats is confined to a restricted post-partum period, the high and stable aggression level and the constancy of its behavioural structure make it an attractive experimental procedure for studying the behavioural effects of psychotropic drugs. Female rats were tested against naive male intruder rats for 5 or 10 min on post-partum days 3–9, during which aggression is stable. Chlordiazepoxide (CDP; 5, 10 and 20 mg/kg, orally) had a biphasic effect on aggression; it increased aggression considerably at 5 and (to a lesser extent) at 10 mg/kg. At 20 mg/kg aggression returned to control level. CDP shortened the latency to the first attack at 5 mg/kg, but not at higher dosages. CDP enhanced aggression, particularly in the first 2 min of an encounter. It did not change the structure of the aggressive behaviour, but did induce a dosedependent increase in feeding. Fluprazine (Flu; 5, 10 and 20 mg/kg IP), a specific antiaggressive (serenic) drug, induced a dose-dependent decrease in aggression and exerted its largest effect in the first 2 min of an encounter. In accordance with the reduced aggression, latencies to the first attack increased. Maternal aggression in rats represents an extension to other (male) aggression paradigms in psychopharmacology. First, it has no male counterpart. Secondly, the hormonal mechanisms underlying this behaviour differ from those of male aggression. Thirdly, the morphology of maternal aggression is different from that shown in male models of agonistic behaviour (e.g. resident-intruder). These features make maternal aggression an attractive paradigm for pharmacological studies of female behaviour.
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  • 74
    ISSN: 1432-2072
    Keywords: 5-HT ; p-Chloroamphetamine ; Zimeldine ; p-Chlorophenylalanine ; Active avoidance ; Acquisition ; Nociception ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract p-Chloramphetamine (PCA, 0.63–5 mg/kg IP) injected 30–60 min before testing produced a dose-related impairment of avoidance acquisition, prolonged reaction time in the hot-plate test and increased locomotor activity. Pretreatment with the selective serotonin (5-HT) uptake inhibitor zimeldine (10 mg/kg IP) blocked these behavioural effects. Degeneration of brain 5-HT neurons by a high neurotoxic dose of PCA (2×10 mg/kg IP) or inhibition of tryptophan hydroxylase by p-chlorophenylalanine (300 mg/kg IP) also blocked the behavioural effects of PCA. There was a complete blockade of the PCA-induced avoidance deficit following pretreatment with metergoline, a central 5-HT receptor blocking agent. On the other hand, metergoline failed to block the hot-plate analgesia and the increased locomotion caused by PCA. Depletion of brain NA and DA by the tyrosine hydroxylase inhibitor H44/68 did not counteract the PCA effect on avoidance or hot-plate performance, but reduced the locomotor stimulating effect. The selective NA neurotoxin DSP4 (50 mg/kg IP) or the opiate antagonist naloxone (1 mg/kg) failed to affect the PCA-induced modulations of the behaviours studied. In addition, PCA administration in doses that caused avoidance deficits, did not result in motor impairment as assessed by the tread mill test. The above results support the hypothesis that the PCA-induced impairment of active avoidance acquisition does not involve changes in nociception or altered locomotor activity. It is concluded that behavioural processes related to serotonergic neurotransmission can be independently modified, suggesting differences in the underlying 5-HT mechanisms.
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  • 75
    ISSN: 1432-2072
    Keywords: Conditioned place preference ; Aversions ; Naloxone ; Morphine ; U50-488 ; β-endorphin ; Dynorphin ; Arcuate nucleus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examines the influence of destruction of the medio-basal arcuate hypothalamus (MBH), the primary site of synthesis of central pools of β-endorphin (β-EP), upon the aversive properties of naloxone in a conditioned place preference paradigm. Bilateral radiofrequency lesions of the MBH resulted in a pronounced fall in levels of immunoreactive β-EP in the brain. Lesioned rats, in contrast to non-operated animals, showed a clear reduction in the conditioned place aversion produced by naloxone. However, they showed no loss of the conditioned preference produced by the mu-selective opioid receptor agonist, morphine, or the conditioned aversion produced by the kappaselective agonist, U50-488. In contrast to the effect of the lesions, suppression of circulating β-EP by dexamethasone treatment failed to influence conditioning produced by naloxone. Thus, the data indicate that the aversive properties of naloxone are attenuated by disruption of central (but not peripheral) β-EP activity. We suggest that these properties of naloxone reflect an antagonism of β-EP activity in the brain. In addition, the data indicate that differing mechanisms underlie the aversive actions of naloxone as compared to U50-488.
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  • 76
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    Keywords: GABAergic hypothesis of anxiolytic action ; Muscimol ; Baclofen ; Chlordiazepoxide ; Picrotoxin ; Bicuculline ; Spontaneous alternation ; Response to stimulus change ; Exploration ; Novelty ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two methods were used to test rats' responses to novelty in the T-maze: (1) a test of spontaneous alternation allowing separate measurement of place and body turn alternation; and (2) a test of entry into an arm of changed brightness (“response to stimulus change”). Chlordiazepoxide reduced spontaneous alternation by specifically weakening body turn alternation and eliminated the response to stimulus change. These findings are similar to those previously reported for the barbiturate sodium amylobarbitone. The same pattern of change in the two tests was seen after a low dose of the GABAA agonist muscimol (0.00125 mg/kg); when the dose of muscimol was raised (0.01 and 0.25 mg/kg), place alternation was also reduced. Picrotoxin but not bicuculline (both GABAA blockers) reversed the effects of muscimol and partially those of chlordiazepoxide on the response to stimulus change; in the spontaneous alternation test picrotoxin only marginally affected the response to 0.25 mg/kg muscimol and actually enhanced the effect of 0.000125 mg/kg. The GABAB agonist baclofen (1 mg/kg) acted in the test of response to stimulus change like chlordiazepoxide and muscimol; however, when baclofen was combined with muscimol, the two drugs tended to show mutual blocking. These results are generally consistent with the hypothesis that GABAergic mechanisms play a role in anxiolytic behavioural activity, but many details are difficult to explain.
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  • 77
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    Keywords: Delayed alternation ; Spatial memory ; Cortex ; Dopamine ; Noradrenaline ; 5-Hydroxytryptamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seventeen male Sprague-Dawley rats were trained to eight to nine correct responses on a delayed spatial alternation test performed on alternate days in a T-maze. Locomotor activity in an observation box was scored on 2 consecutive days. The animals were killed 2 weeks after the end of behavioural testing and dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5HT), the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the 5HT metabolite, 5-hydroxyindoleacetic acid (5HIAA) determined in cortex, hippocampus, striatum and hypothalamus. Cortical concentrations of both DA and NA correlated negatively and significantly with the number of errors made in learning the alternation task, though the latter correlation was less striking and became negligible after the correlation between DA and NA was partialled out. Concentrations of DA and NA in the other regions did not correlate significantly with errors. None of the other neurochemical variables correlated significantly with either errors or locomotor activity, except for hypothalamic HVA concentration which showed a marginally significant correlation with locomotor activity. The above results, together with effects of brain lesions reported by other authors, strongly indicate that cortical catecholamines facilitate learning in the normal non-drug-treated rat.
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  • 78
    ISSN: 1432-2072
    Keywords: Dopamine ; D-1 and D-2 receptors ; SCH 23390 ; RU24213 ; Stereotypy ; 5-Hydroxytryptamine ; Ro22-2586 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of the putative selective dopamine D-1 antagonist benzazepine SCH 23390 and of the selective dopamine D-2 antagonist Ro22-2586 on stereotypy induced by the selective D-2 agonist RU24213 were compared. RU24213 (0.5–15 mg/kg) dose-dependently induced stereotyped behaviour characterised by continuous downward sniffing and locomotion. These responses were antagonised, as expected, by 40–200 μg/kg Ro22-2586, but surprisingly blocked by 40–200 μg/kg SCH 23390. The selectivities of these compounds for dopamine receptor subtypes were verified in terms of their relative abilities to displace the in vitro binding of 3H-piflutixol to striatal D-1 receptors and of 3H-spiperone to D-2 receptors. As SCH 23390 fails to influence D-2 mediated prolactin secretion or emesis in vivo, there appears to be no significant formation of an active metabolite of SCH 23390 with D-2 antagonist activity. Because SCH 23390 has some affinity for 5-hydroxytryptamine receptors, any effect on the serotonergic behavioural syndrome induced by 10 mg/kg 5-methoxy-N,N-dimethyltryptamine was also studied. The serotonergic responses of hind limb abduction, reciprocal forepaw treading and Straub tail were unaltered after 40–200 μg/kg SCH 23390, indicating no significant 5-HT blockade or non-specific depressant action at these doses which might influence the expression of stereotypy. Thus, these data are consistent with blockade of tonic D-1 dopaminergic activity that may influence the expression of behaviours initiated byD-2 dopaminergic stimulation.
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    Psychopharmacology 87 (1985), S. 328-333 
    ISSN: 1432-2072
    Keywords: Khat ; Cathinone ; Amphetamine ; Conditioned taste aversion ; Adipsia ; Toxicity ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The potency of dl-cathinone (the active constituent of the Khat plant) was compared with that of d-amphetamine in the conditioned taste aversion (C. T. A.) procedure and in a test of drug-induced adipsia in rats. Both drugs induced C.T.A., the potency ratio being 1∶17 (amphetamine was more potent). Both drugs induced adipsia in deprived rats given access to water for 120 min. The potency ratio in this procedure was 1∶4. Potency in the C.T.A. procedure did not therefore correlate with potency in inducing adipsia; consequently drug-induced C.T.A. cannot be attributed to conditioned adipsia. In the adipsia test the drugs had similar durations of action, thus factors related to duration of drug action (cf Cappell and Le Blanc 1977) cannot account for the surprisingly low potency of cathinone in the C.T.A. procedure. These data, obtained with stimulant drugs with similar structures and similar actions in a variety of conventional in vivo and in vitro pharmacological tests, illustrate the unpredictable nature of drug actions in the C.T.A. procedure. The low potency of cathinone in inducing C.T.A. could not be predicted from knowledge of the potency of this compound in tests of adipsia (as shown here) or (as reported elsewhere) in tests of anorexia, locomotor stimulation, stereotypy, suppression of operant responding, drug discrimination, release and inhibition of reuptake of dopamine and noradrenaline, lethality and actions on the cardiovascular system. All of these studies have reported potency ratios considerably lower than 1∶17, which were nevertheless similar to the 1∶4 ratio observed in the adipsia test. It is suggested that the weak potency of cathinone in the C.T.A. procedure may be related to its comparatively potent reinforcing actions in the self-administration procedure.
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  • 80
    ISSN: 1432-2072
    Keywords: EEG ; Pentylenetetrazol ; Antiepileptic drugs ; Cluster analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to validate a new animal model predictive of the profile of antiepileptic drugs, we studied the antagonism by standard antiepileptics of the EEG modifications induced by low-speed IV infusion of pentylenetetrazol (PTZ) in rats. The activity of the drugs was measured by their effects on temporal characteristics of the PTZ-induced EEG paroxysms. Most compounds had moderate to potent anti-PTZ effects, as shown by the changes in the EEG temporal parameters. However, these effects depended on the drugs and doses. Cluster analysis showed that drugs and doses which evoked similar changes were closely related and were included in separate clusters with respect to one another. In particular, the present results showed that benzodiazepines and antiepileptics cluster differently in their effects. Thus, this model could be a useful tool for assessing new antiepileptic drugs.
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    Psychopharmacology 87 (1985), S. 351-356 
    ISSN: 1432-2072
    Keywords: Apomorphine ; Haloperidol ; Thioridazine ; Central drug administration ; Dopamine ; Feeding behaviour ; Microstructural analysis ; Eating rate ; Eating time ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anorectic effects of apomorphine were studied in a microstructural analysis paradigm. Low doses of apomorphine (〈0.1 mg/kg SC) reduced food intake, by reducting both the rate of eating and eating time. The neuroleptics haloperidol and thioridazine blocked the effect of apomorphine on eating time, but not on eating rate. Anorectic effects elicited by apomorphine administration to the ventral tegmental area and, to a lesser extent, the substantia nigra were mediated by a selective reduction of eating time. Effects of apomorphine on eating time appear to result from an action at presynaptic dopamine receptors; the mechanism of the effect of apomorphine on eating rate is unclear.
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    Psychopharmacology 87 (1985), S. 357-363 
    ISSN: 1432-2072
    Keywords: Delayed matching ; Short-term memory ; Cholinergic systems ; Nucleus basalis ; Fimbria-fornix ; Scopolamine ; Physostigmine ; Methamphetamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To provide a more specific test of memory impairments following lesions to central cholinergic systems, rats were trained on an operant delayed matching task. Ibotenic acid lesions of the nucleus basalis produced a disruption of performance at all delay intervals (a parallel downward shift in the delay-performance curve). By contrast, fimbriafornix transections had no effects at short delays, but produced a progressively greater impairment as the delays lengthened (an increased downward slope of the delay-performance curve). Scopolamine produced a dose-dependent disruption of performance, apparent at the shortest delays but greater at longer delays, that was similar to the two lesion deficits combined, whereas physostigmine induced a mild but significant enhancement of performance. The results support the hypothesis that disruption of hippocampal circuitries, including cholinergic afferents via the fimbria-fornix, produces short-term or working memory impairments, whereas disruption of the cortical cholinergic system implicates more stable long-term aspects of task performance. Peripherally administered cholinergic drugs produce both types of effect and thus may influence both systems.
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  • 83
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    Psychopharmacology 87 (1985), S. 368-370 
    ISSN: 1432-2072
    Keywords: Dopamine receptors ; Drug discrimination ; Rat ; SKF 38393 ; SKF 82526
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats (N=11) were trained to discriminate SKF 38393 (8.0 mg/kg, IP), a D1 dopamine receptor agonist, from saline in a two-lever, food-reinforced (FR 30) drug discrimination paradigm. The discrimination was acquired by nine rats within an average of 77±6 (SEM) sessions. Subsequently, various doses of SKF 38393 as well as SKF 82526, a potent, selective D1 agonist that does not readily penetrate the blood-brain barrier, were injected prior to test sessions. SKF 38393 (2–16 mg/kg) produced a dose-related increase in the percent of responses that occurred on the drug lever during test sessions. On the other hand, SKF 82526 (0.125 and 1.0 mg/kg) induced no drugappropriate responding. This experiment establishes that SKF 38393 can serve as a discriminative stimulus in rats. Furthermore, the observation that SKF 82526 did not substitute for SKF 38393 in this paradigm makes it unlikely that this effect involves a peripheral site of action. The results suggest the existence of a functional, behaviorally relevant D1 dopamine receptor in the CNS of rats.
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  • 84
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    Psychopharmacology 87 (1985), S. 425-429 
    ISSN: 1432-2072
    Keywords: Morphine ; Clonidine ; l-Nantradol ; Tolerance ; Shock avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interruption of a photobeam by rats was maintained under a continuous shock avoidance schedule, and moderate response rates were maintained at low shock frequencies. Responding decreased, and shock frequency increased, in a dose-dependent manner after acute injections of the narcotic morphine, the antihypertensive l-nantradol clonidine, and the cannabinoid l-nantradol. Clonidine and l-nantradol were about 100 times more potent than morphine for decreasing overall responding, and l-nantradol was about 3 times more potent than clonidine for decreasing escape responding. When drugs were given repeatedly prior to daily experimental sessions, tolerance developed to response rate decreases of morphine and l-nantradol within seven to ten sessions, but tolerance did not develop to rate decreases of clonidine for up to 30 sessions. Continued decreased responding by clonidine was antagonized by yohimbine, but not by prazosin or naltrexone. These results extend observations for the acute effects of l-nantradol and clonidine to operant responding under a schedule of continuous shock avoidance. Different potencies for drugs in the present and previous experiments suggest important effects of response topography on dose effects.
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  • 85
    ISSN: 1432-2072
    Keywords: Arginine vasopressin ; EEG ; Spectral analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several studies have suggested that arginine vasopressin (AVP) may act centrally as a neurohormone or neuromodulator to produce electrophysiological and behavioral effects. However, there are few reports of EEG effects of AVP in unanesthetized, behaving animals. In the present study the EEG effects of “behaviorally relevant” subcutaneous (SC) doses of AVP (6 μg/kg) known to raise blood pressure were compared to “behaviorally relevant” intracerebroventricular (ICV) doses (0.1–1.0 ng) and multiple “toxic” ICV doses (1.0 μg) of AVP. Central injections of toxic doses of AVP produced behavioral arrest, bodily barrel rolling, and EEG slowing, but did not induce electrographic signs of seizure activity. Comparison of the spectral characteristics of the EEG revealed some similarities in the distribution of power between SC and the 1.0 ng ICV dose; whereas ICV doses of 0.1 and 0.5 ng produced power distributions that were different from those seen following saline or SC doses of AVP. The similarities in EEG activity between SC injections and the 1.0 ng ICV dose suggest a common brain state may be induced by the two routes of administration in those dose ranges.
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  • 86
    ISSN: 1432-2072
    Keywords: Habenula ; Behavioural despair ; Nomifensine ; Swimming behaviour ; Stress ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Lister rats with bilateral lesions of the habenula nuclei were observed during two consecutive phases of a swim test. During the first phase of the test, when escape was not possible, lesioned animals demonstrated fewer changes of behaviour. Lesioned animals failed to utilise an introduced external cue and escape route in the second part of the test. Control rats treated with the antidepressant nomifensine showed few changes of behaviour during the inescapable phase of the test but an enhanced ability to escape. Nomifensine produced no improvement of escape behaviour in lesioned animals, suggesting that this behavioural effect of nomifensine in controls is dependent on the habenula relay. The data also suggest that more than one response in swim tests can serve as an index of depression.
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  • 87
    ISSN: 1432-2072
    Keywords: Morphine analgesic tolerance ; Environment distinctiveness ; Habituation ; Compensatory conditioning ; Overshadowing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The experiments reported here investigated the mechanisms of drug tolerance acquisition in environments differing in distinctiveness. Specifically, they examined the hypothesis that tolerance acquired in non-distinctive environments might involve habituation while tolerance acquired in distinctive environments involves a classical conditioning or associative learning mechanism. In Experiment 1, rats pre-exposed to injection-ritual cues (placebo injections) prior to acquisition of tolerance to morphine analgesia in distinctive or non-distinctive environments showed a typically attenuated tolerance response on an environment-change test. The magnitude of the attentuation was not affected by the distinctiveness of the acquisition environment. In Experiment 2, rats acquiring tolerance in distinctive or non-distinctive environments, but without prior injection-ritual pre-exposure, did not demonstrate an attenuation of tolerance on an environment-change test. Tolerance acquired in either environment was unaffected by a subsequent rest period in the colony room, but was attenuated by a subsequent period of daily placebo injections in the colony room. It is argued that failure to observe environment-specific tolerance, as in Experiment 2 and in previous reports in the literature, may reflect overshadowing of environmental stimuli by injection-ritual stimuli, and are not indicative of a fundamental difference between the mechanisms of tolerance acquisition in environments varying in distinctiveness.
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  • 88
    ISSN: 1432-2072
    Keywords: Exploration ; Locomotor activity ; Sedation ; Chlordiazepoxide ; Benzodiazepine ; CL 218,872 ; Benzodiazepine antagonists ; Ro 15-1788 ; CGS 8216 ; Rat ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of CL 218,872, initially classified as a non-sedative anxiolytic, were investigated and compared with those of chlordiazepoxide in the holeboard. The ability of two drugs that antagonise the effects of benzodiazepines, CGS 8216 and Ro 15-1788, to reverse the effects of CL 218,872 and chlordiazepoxide were also investigated, to see whether their effects might be mediated via benzodiazepine receptors. CL 218,872 (10 mg/kg) was found to be significantly sedative in both mice and rats (i.e., both locomotor activity and head-dipping were significantly decreased). In mice, the effects of CL 218,872 and of chlordiazepoxide were very similar over a range of doses, except that the stimulatory effect seen with low doses of chlordiazepoxide on head-dipping just failed to reach significance with CL 218,872. This study is in agreement with recently published results from different tests showing that sedative effects can be obtained with doses of CL 218,872 that are low and not much higher than those leading to anxiolysis. The sedative effects of both CL 218,872 (10 mg/kg) and chlordiazepoxide (20 mg/kg) were significantly reversed by RO 15-1788 (10 and 20 mg/kg) and CGS 8216 (10 mg/kg), suggesting that their effects are mediated via benzodiazepine receptors. The increase in head-dipping seen with chlordiazepoxide (2.5 mg/kg) was also reversed by RO 15-1788 and CGS 8216.
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  • 89
    ISSN: 1432-2072
    Keywords: DA D-1 receptors ; DA D-2 receptors ; Circling behaviour ; Dopamine agonists ; Dopamine antagonists ; 6-OHDA lesions ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The antagonistic effect of dopamine (DA) D-1 and D-2 antagonists against circling behaviour induced by various DA agonists in 6-OHDA-lesioned rats has been investigated. DA D-1/D-2 selectivity of agonists in vitro was measured by the stimulatory effect on DA-sensitive adenylate cyclase in rat striatal homogenates (D-1), the inhibitory effect on electrically-induced release of 3H-DA in rabbit striatal slices (D-2) and the affinity to 3H-piflutixol (D-1) and 3H-spiroperidol (D-2) binding sites in rat striatal membranes. The contralateral circling behaviour induced by the DA D-1 agonist SK & F 38393 was blocked by the DA D-1 antagonist, SCH 23390, and by the mixed DA D-1/D-2 antagonist cis(Z)-flupentixol, but was not influenced by the DA D-2 antagonists spiroperidol and clebopride. In contrast, circling behaviour induced by the preferential DA D-2 agonists pergolide and LY 171555 was blocked by clebopride, spiroperidol, and cis(Z)-flupentixol, but weakly or not influenced by SCH 23390. Apomorphine-induced circling behaviour was blocked by cis(Z)-flupentixol, partially antagonized by SCH 23390 and clebopride but not inhibited by spiroperidol, although the time-course of circling was changed. Combinations of SCH 23390 with spiroperidol or clebopride in low doses completely blocked the effect of apomorphine. These results indicate that DA D-1 and D-2 receptors mediate circling behaviour through separate mechanisms which can be independently manipulated with respective agonists and antagonists. Furthermore, the results indicate that both DA D-1 and D-2 receptors are involved in the effect of apomorphine, since selective antagonists induced maximally 50% inhibition. Complete blockade was only found in combination experiments and by the mixed D-1/D-2 antagonists cis(Z)-flupentixol, cis(Z)-clopenthixol, and clozapine.
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  • 90
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    Psychopharmacology 86 (1985), S. 81-83 
    ISSN: 1432-2072
    Keywords: Chlorpromazine ; Haloperidol ; Conditioned taste aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using in rats a Conditioned Taste Aversion (CTA) procedure, chlorpromazine was shown to possess significant US properties at the highest dose tested (8 mg/kg IP repeated four times). In contrast, haloperidol failed to exert a similar effect at a dosage (1.6 mg/kg IPx4) at least twice as high, in terms of pharmacological activity, as the effective chlorpromazine dosage. These data suggest that the induction of neuroleptic extrapyramidal side effects and the antidopaminergic properties shared by the two drugs may not be responsible for the aversive effect of chlorpromazine. However, it cannot be excluded than haloperidol produces an aversion which is antagonized by some action of the drug not shared by chlorpromazine.
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  • 91
    ISSN: 1432-2072
    Keywords: Chlorpromazine ; Lithium chloride ; Conditioned Taste Aversion ; Extinction ; Housing condition ; Isolation ; Social behaviour ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were used in two experiments to investigate the influence of social variables on the acquisition of Conditioned Taste Aversion (CTA) to either lithium chloride (10 ml/kg IP of a 0.3-M solution given twice) or chlorpromazine (8 mg/kg IP given four times) and on subsequent extinction. CTA acquisition was not affected by original housing assignment (isolation or paired housing for 15–23 days prior to conditioning), by the shifted social assignment during conditioning, or by the drugged state of the paired animals' partners on drug-scheduled days. However, for both drugs, permanently isolated animals extinguished CTA more slowly than rats housed permanently in pairs. Shifts from isolation to pairing or vice versa failed to alter CTA extinction in the case of lithium, but affected it significantly in chlorpromazine-treated rats. Shifts from isolation to paired housing with an undrugged partner produced faster extinction for lithium than the corresponding group with a drugged partner. For chlorpromazine, the effect of the same shift was exactly the opposite. Overall, the results show that changes in CTA extinction can be a function of social variables.
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  • 92
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    Psychopharmacology 85 (1985), S. 469-475 
    ISSN: 1432-2072
    Keywords: 8-OH-DPAT ; Lisuride ; Ergot derivatives ; Acoustic startle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Five ergot-related compounds were examined for their effects on the acoustic startle response in the rat. The startle amplitude and the startle latency were registered. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 0.5–8 mg/kg) and lisuride (0.05–0.8 mg/kg) were found to enhance the startle amplitude, while the mainly DA receptor active ergot derivatives pergolide (0.2–0.8 mg/kg), bromocriptine (5–20 mg/kg) and LY 141865 (5–20 mg/kg) had no, or even the reverse, effect. All five compounds caused a prolongation of the startle latency. The increased startle amplitude caused by 8-OH-DPAT (2 mg/kg) and lisuride (0.2 mg/kg) was successfully antagonized by the 5-HT receptor antagonist methiothepin (0.1 mg/kg) but not by metergoline (1 mg/kg). 5-Hydroxy-L-tryptophan (L-5-HTP; 12.5–50 mg/kg), administered to pargyline- and benserazide-pretreated animals, was included for comparison. The serotonin precursor caused a marked increase in the startle amplitude and a shortening of the startle latency.
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  • 93
    ISSN: 1432-2072
    Keywords: Nucleus accumbens ; Noradrenaline ; Dopamine ; Serotonin ; Monoaminergic agonists ; Open field locomotor activity ; Forced swim test ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intraaccumbens injections of catecholamines noradrenaline and dopamine, though not of serotonin, stimulated locomotion by rats in an open field, 10–15 min later. Similar effects were observed 5 min after microinjection of apomorphine whereas clonidine only attenuated locomotor activity. On the other hand, intraaccumbens administration of phenylephrine, isoproterenol and quipazine, in doses similar to an effective dose of noradrenaline, did not alter rat open field behavior. The escape-directed activity of rats in the forced swim test (FST) was stimulated 5 min after local administration of noradrenaline, phenylephrine, isoproterenol or apomorphine only. No effects in the FST were observed 15 min after noradrenaline injection or after intracaudate noradrenaline administration. The stimulatory effects of intraaccumbens noradrenaline injection in the FST were antagonized by the local pretreatment of rats with phentolamine, though not with propranolol. Accordingly, it is possible to conclude that both catecholamines, but not serotonin, play complex and probably distinct roles within the nucleus accumbens in the stimulation of activity by rats in the FST and the open field test.
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  • 94
    ISSN: 1432-0738
    Keywords: 2,4,6-Trinitrotoluene ; Carcinogens ; 2,4-Dinitrotoluene ; Rat ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 2,4,6-Trinitrotoluene (TNT) is structurally related to the rat liver carcinogen 2,4-dinitrotoluene (technical grade), and both compounds are known to be mutagenic to bacteria in vitro. TNT is therefore established as a potential rodent carcinogen; the present paper describes experiments designed to assess if this potential is likely to be expressed in appropriately exposed animals. TNT gave a negative response in the mouse bone marrow micronucleus assay and in an in vivo/in vitro rat liver assay for unscheduled DNA synthesis (UDS). In the latter assay animals are exposed to the test chemical in vivo and their hepatocytes subsequently evaluated for UDS in vitro. The negative response observed for TNT in the liver assay at dose-levels up to 1000 mg/kg was accompanied by a positive response for the hepatocarcinogen 2,4-dinitrotoluene at the lower dose-level of 200 mg/kg. In contrast, the dinitro compound gave a negative response in the micronucleus assay, as was also observed for TNT. It is concluded that the negative response observed for TNT in the liver assay indicates that it is unlikely to be a rat hepatocarcinogen. Nonetheless, high levels of methaemoglobin were observed in the TNT-treated rats and their urine was coloured red. These facts, together with the known toxicities of this agent suggest a possible carcinogenic hazard to the haemopoetic and urinary tissues of animals exposed chronically to it at toxic dose-levels.
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  • 95
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    Archives of toxicology 57 (1985), S. 226-230 
    ISSN: 1432-0738
    Keywords: Di-(2-ethylhexyl) phthalate ; Mono-(2-ethylhexyl) phthalate ; Plasma level ; Disposition ; Oral dose ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The dispositon of di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) was studied in the rat. Three hours after a single oral dose of DEHP (2.8 g/kg), plasma concentrations of 8.8±1.7 μg/ml DEHP and 63.2±8.7 μg/ml MEHP were reached. MEHP levels declined with a half-life of 5.2±0.5 h. The ratio of the area under the plasma concentration-time curve of MEHP to that of DEHP was 16.1±6.1. When 14CDEHP was administered, 19.3±3.3% of the radioactivity was excreted in the urine within 72 h, the rest being excreted in the faeces. The urinary excretion rate of total radioactivity declined with a half-life of 7.9±0.5 h. Single administration of MEHP (0.4 g/kg) resulted in plasma concentrations of 84.1±14.9 μg/ml 3 h after dosing; the half-life of MEHP was 5.5±1.1 h. Multiple dosing with DEHP (2.8 g/kg/day) for 7 consecutive days produced no accumulation of DEHP or MEHP in plasma.
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  • 96
    ISSN: 1432-0738
    Keywords: Thiabendazole ; Adenosine triphosphate ; Teratogenesis ; Mouse ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ogata et al. (1984) reported that thiabendazole (TBZ) was teratogenic in mice when olive oil was used as a vehicle, but not teratogenic when administered in gum arabic. Results of investigations into the possible association between TBZ-induced teratogenicity and adenosine triphosphate (ATP) are reported here. ATP levels in the limb buds were measured at day 10 of gestation in controls and mice treated with 1300 mg/kg TBZ 24 h previously. The results showed that there was a correlation between the dosage of TBZ and the ATP levels of fore and hind limb buds (r=−0.827 and r=−0.799, respectively). ATP levels in mouse limbs were reduced to 22–31% of control values when TBZ was given in olive oil, but the ATP reduction was only 6–9% when TBZ was given in gum arabic. This suggests that there may be a relationship between the teratogenic and ATP-depressing action of TBZ on the limb buds of mouse embryos. Pregnant rats were also treated with TBZ. TBZ at a dose level of 1000 mg/kg was given orally on day 11 of gestation. After 24 h, ATP levels in fetal rat limbs were still 82% of control values. These results confirm the observations of Ogata et al. on the vehicle effect and the difference in response between mice and rats.
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  • 97
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    Archives of toxicology 56 (1985), S. 252-255 
    ISSN: 1432-0738
    Keywords: Cadmium ; Selenium ; Liver ; Kidney ; Rat ; Metallothionein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In acute studies, approximately 70–90% of cytosolic cadmium in liver and kidney has been shown to be bound to metallothionein, a low-molecular weight protein. In this study, we report on the influence of dietary selenium on the distribution of cadmium in rat kidney and liver. Contrary to the findings of most acute studies, our results indicate that only a relatively small proportion of cadmium (approximately 14% in the kidney and 44% in the liver) is bound to metallothionein when cadmium is administered for 7 weeks in the diet and via osmotic minipumps to selenium-deficient rats. Feeding rats the same diet supplemented with 1.0 ppm selenium results in no detectable cadmium-metallothionein peak in the kidney, and only about 10% of the cytosolic cadmium elutes as cadmium bound to metallothionein in the liver. In animals fed the selenium-supplemented diet, the bulk of the cadmium is recovered in the low-molecular weight fraction. Dietary selenium did not significantly affect the distribution of zinc and copper in the kidney or liver.
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  • 98
    ISSN: 1432-0738
    Keywords: 1-Deamino-2-tyr(ethyl) oxytocin (dEtOT) ; Peri-and postnatal effect ; Growth retardation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of 1-deamino-2-tyr(ethyl) oxytocin (dEtOT) upon peri- and postnatal development of the rat was studied in two experiments when administered between day 15 of pregnancy and the day of parturition. The investigation showed that dEtOT did not affect the pups at birth, that dEtOT caused a dose-related growth retardation of the pups, that the growth inhibiting effect was directly correlated to the length of administration and that the growth inhibiting effect was more pronounced if dEtOT was given close to parturition than if it was given earlier in the pregnancy. In addition, the growth retardation was not due to an effect on the pups but to an effect on their mothers, probably related to inhibition of the emptying mechanisms of the mammary glands, meaning that the pups were insufficiently fed by their mothers immediately after birth.
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  • 99
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    Archives of toxicology 56 (1985), S. 167-169 
    ISSN: 1432-0738
    Keywords: Heavy metal salts ; Mixed function oxidases ; Cytochrome P-450 ; ALA synthetase ; Heme oxygenase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of Co(NO3)2, CdSO4, NiSO4, ZnSO4, and HgCl2 (given repeatedly in subtoxic doses in the drinking water for 30 days) on rat liver monooxygenases was studied in experiments on male Wistar rats. The salts of Co, Cd, and Zn increased the activity of benzphetamine-N-demethylase, the content of cytochrome P-450 and microsomal heme. The data suggest that these salts exert an enzyme-inducing effect on the hepatic monooxygenases. The same metal salts (Co, Cd, and Zn) increased the activity of δ-aminolevulinic acid (ALA) synthetase and decreased that of heme oxygenase. The increased cytochrome P-450 content is probably due to the increased synthesis and the decreased breakdown of this hemoprotein. HgCl2 and NiSO4 did not exert an enzyme-inducing action. The lack of change in the activity of NADPH-cytochrome c reductase and cytochrome b5 (except for ZnSO4) suggests that these components of the electron transport chain are not likely to be involved in the enzyme-inducing action of the heavy metal salts.
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  • 100
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    Archives of toxicology 56 (1985), S. 204-206 
    ISSN: 1432-0738
    Keywords: Peripheral neuropathy ; 2,5-hexanedione ; Conduction velocity ; Distal latency ; Vitamin B12 ; Vitamin B6 ; Therapeutic effects ; Rat ; Tail nerve
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The therapeutic effect of Vitamin B12 or Vitamin B6 on 2,5-hexanedione induced-neuropathy in animals was examined by using our electrodiagnostic technique in order to investigate the mechanism of the development of the neuropathy. Pyridoxal phosphate and two forms of Vitamin B12 were administered to rats intoxicated by the neurotoxin for a period of 18 weeks, and the sensory and motor fiber conduction velocity and the motor distal latency of the tail nerve were periodically determined. None of the groups treated with the therapeutic drugs exhibited a definite improvement in the nerve fiber conduction velocity and motor distal latency of the rat tail nerve, as compared with those of the 2,5-hexane-dione-treated controls.
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