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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 95 (1988), S. 413-417 
    ISSN: 1432-2072
    Keywords: DRL-schedule ; Imipramine ; Mianserin ; Idazoxan ; Yohimbine ; Amphetamine ; α2-Adrenoceptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have reported that antidepressant drugs exert specific effects on responding maintained by DRL schedules of reinforcement, giving rise to increased frequencies of reinforcement. In order to investigate whether the α2-adrenoceptor antagonist idazoxan would produce similar effects, the actions of this compound were compared with those of yohimbine, imipramine, mianserin and d-amphetamine in rats trained to lever press for food reinforcement on a DRL 60-s schedule. Neither imipramine nor mianserin produced any effects on response rate or reinforcement frequency, except at the highest doses. In contrast, both idazoxan and yohimbine gave rise to dose-related increases in rates of responding and consequent decreases in reinforcement frequencies. Amphetamine also increased responding, but higher doses of this drug produced marked hyperactivity and stereotyped movements which were not observed after idazoxan and yohimbine. Although the present behavioural baseline was not sensitive to antidepressants, it demonstrated an unexpected activity of two α2-adrenoceptor antagonists which deserves further investigation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 99 (1989), S. 117-121 
    ISSN: 1432-2072
    Keywords: Idazoxan ; Drug discrimination ; Yohimbine ; Buspirone ; α2-Adrenoceptors ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate a dose of the α2-adrenoceptor antagonist idazoxan (10 mg/kg IP) from saline. The discriminative stimulus produced by idazoxan was dose related and generalised to yohimbine. However, generalisation did not occur with a variety of compounds from other pharmacological categories including the α1-adrenoceptor agonist cirazoline, the α2-adrenoceptor antagonist prazosin, and the α2-adrenoceptor agonist clonidine. The idazoxan stimulus was not antagonised by either prazosin or clonidine, although it was clear that idazoxan antagonised the reductions in response rate produced by clonidine. Dose-related responding on the idazoxan-associated lever was produced by the anxiolytics buspirone and ipsapirone and by their metabolite MJ 13653 (1-PP), which has previously been shown to be an α2-adrenoceptor antagonist. In general, however, high levels of generalisation occurred with these three compounds only at doses which substantially reduced response rates. These results demonstrate that idazoxan can give rise to a discriminative stimulus which is probably mediated through antagonism at α2-adrenoceptors although the failure of clonidine to block the idazoxan stimulus is difficult to explain.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Chlordiazepoxide ; Zolpidem ; Ro 16-6028 ; Ro 17-1812 ; Drug discrimination ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of Ro 16-6028 and Ro 17-1812, two novel benzodiazepines with mixed agonist and antagonist properties, were studied in rats trained to discriminate either chlordiazepoxide or the benzodiazepine receptor ligand zolpidem. In rats discriminating 5 mg/kg chlordiazepoxide from saline both Ro 16-6028 and Ro 17-1812 produced responding on the drug lever. At a dose of 10 mg/kg both compounds gave rise to 100% responding on the lever associated with chlordiazepoxide. The dose-response curve produced by Ro 16-6028 was flatter than that for Ro 17-1812, however. The discriminative cue produced by 2 mg/kg zolpidem did not generalise to either Ro 16-6028 or Ro 17-1812. In contrast, both of those compounds antagonised the zolpidem cue and also antagonised the reduction in response rates produced by zolpidem. These results are consistent with previous findings that Ro 16-6028 and Ro 17-1812 may exert anxiolytic-like effects typical of benzodiazepines while antagonising the depressant actions of benzodiazepine receptor ligands. The results are also consistent with the suggestion that the discriminative cues produced by chlordiazepoxide and zolpidem may be mediated, at least partially, by activity at different sub-types of benzodiazepine receptors.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Rat ; Drug discrimination ; NMDA ; Phencyelidine ; ±SKF 10047 ; MK 801 ; CPP ; Ifenprodil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate phencyclidine (PCP) from saline at doses of 2 and 4 mg/kg, using a two-lever food reinforced operant technique. ±N-allylnormetazocine (±SKF 10047), +5-methyl-10,11-dihydro-5H-dibenzo[A,D]cyclohepten-5,10-imine (MK 801), 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP) and ifenprodil, which have been shown to antagonise the effects of N-methyl-d-aspartate (NMDA), were tested for their ability to give rise to PCP-appropriate responding. In rats trained at both doses of PCP, ±SKF 10047 (2–12 mg/kg) and MK 801 (0.0125–0.2 mg/kg) produced dose-related responding on the lever associated with PCP injection. The relative potency of these two compounds was the same in the two groups of animals, but their absolute potencies to produce a PCP-like discriminative stimulus were dependent on the training dose of PCP. In contrast, neither the competitive NMDA antagonist CPP (4–20 mg/kg) nor the non-competitive antagonist ifenprodil (2–12 mg/kg) produced PCP-appropriate responding and ifenprodil (4-mg/kg) neither potentiated nor antagonised PCP. These findings are discussed in the light of the hypothesis that the behavioural effects of PCP are mediated via a reduction of neurotransmission at the NMDA-subtype of glutamate receptors.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Key words Apomorphine ; 7-OH-DPAT ; Drug discrimination ; Dopamine D3 receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have reported that the non-selective dopamine agonist, apomorphine, can serve effectively as a discriminative stimulus in experimental animals, and evidence has been presented that this effect is mediated by dopamine D2 receptors. More recently, it has been found that another dopamine agonist, 7-OH-DPAT, which has some selectivity for D3 receptors, also produces a discriminative cue in rats. The present study set out to make a direct comparison of the discriminative stimulus effects of these two compounds. Rats were trained to discriminate either apomorphine (0.05 mg/kg, SC) or 7-OH-DPAT (0.1 mg/kg, IP) from saline. Both discriminations were acquired but extended training was necessary. Cross generalisation occurred between the two compounds and both cues generalised to the dopamine agonists, quinpirole, quinelorane, PD 128207, and bromocriptine. When the potencies of these compounds to produce the apomorphine or 7-OH-DPAT cues were correlated with their potencies to produce D2 or D3 functional responses in vitro (mitogenesis in transfected cells–results taken from the literature) stronger correlations with D3 than with D2 responses were observed. Both the cueing and the response rate-decreasing effects of apomorphine and 7-OH-DPAT were antagonised by the autoreceptor selective dopamine antagonist amisulpride, and sulpiride also antagonised the cues but without affecting response rates. In contrast, haloperidol blocked the cues but potentiated the response rate decreases. These results suggest that, at the doses used, apomorphine and 7-OH-DPAT produce similar discriminative stimuli, which may be mediated by presynaptically located dopamine D3 receptors.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 104 (1991), S. 27-34 
    ISSN: 1432-2072
    Keywords: Learning ; NMDA receptors ; Memory ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent studies have shown that several compounds known to act as competitive or non-competitive antagonists of NMDA receptors can disrupt learning in rodents. The present study was carried out to investigate the effects of a range of NMDA antagonists, acting at several sites in the NMDA receptor complex, on the acquisition of learned fear in mice. Dose-related disruptions of learning were produced by the non-competitive antagonists phencyclidine, dizocilpine, dextromethorphan and (+) and (−)N-allylnormetazocine. The (+) enantiomer of N-allylnormetazocine was approximately twice as potent as the (−) enantiomer. The competitive NMDA receptor antagonist, CGS 19755, also blocked the acquisition of learned fear as did the non-specific glutamate antagonist riluzole. In contrast, the antiischaemic drugs ifenprodil and SL 82.0715, which probably act as NMDA antagonists through an effect on the polyamine site, had no effect on learning up to doses which substantially reduced locomotion. The sigma receptor ligand DTG was also inactive. These results confirm that both competitive and non-competitive NMDA antagonists disrupt learning but indicate that the extent to which such an effect is observed may depend on the site at which the compounds act within the receptor complex. Activity at sigma receptors is unrelated to the effect on learning.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2072
    Keywords: Key words Anxiety ; Benzodiazepine ; Diazepam ; Elevated plus-maze ; Inbred and outbred mouse strains ; Light/dark test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Natural strain differences exist in mice for behavioural traits such as emotional reactivity. Objective: The present experiments compared the behavioural profiles of nine strains of mice (BALB/c, C57BL/6, C3H, CBA, DBA/2, NMRI, NZB, SJL, Swiss) in two models of anxiety after the administration of the benzodiazepine diazepam. Methods: The tests used were the light/dark choice task and the elevated plus-maze, two well-validated anxiolytic screening tests. Results: In vehicle-treated animals, differences on variables designed to measure anxiety-related behaviours were observed in both tests. In the light/dark test, the strains could be divided into three distinct groups: two non-reactive strains (NZB and SJL), an intermediate-reactive group (C3H, CBA, DBA/2, NMRI, C57BL/6 and Swiss), and one highly reactive strain (BALB/c). In the elevated plus-maze, SJL, NMRI, CBA and, to a lesser extent, C3H strains of mice, consistently showed low levels of anxiety-related behaviours. Intermediate levels were seen in the Swiss and BALB/c strains, and high levels of emotional reactivity were seen in C57BL/6, DBA/2 and NZB. The strain distribution between the light/dark and the elevated plus-maze tests shows similarities and differences, suggesting that each of these experimental procedures represents a different set of behaviours. Marked differences between a number of strains of mice in their sensitivity to the anxiolytic-like action of diazepam were observed in both the light/dark and the elevated plus-maze tests. Mice of the BALB/c, Swiss and, to a lesser extent, CBA and C3H strains were responsive to diazepam in both tests, although in the case of CBA mice, effects may have been contaminated by behavioural suppression. SJL mice were largely unresponsive to the action of the benzodiazepine in both tests, whereas in C57, DBA/2, NMRI and NZB mice, diazepam produced positive effects only in the elevated plus-maze. Conclusion: The finding of differential strain distributions both with and without diazepam treatment in the light/dark and the elevated plus-maze tests, indicates that not all strains of mice are suitable for investigating the effects of GABA/BZ receptor ligands. This study may thus provide a useful guide for choosing the best strain of mice for studying the pharmacology of fear-related behaviours.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 48 (1976), S. 307-309 
    ISSN: 1432-2072
    Keywords: Scopolamine ; Physostigmine ; Adjunctive drinking ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nine, food-deprived rats were each given daily sessions during which 60 45-mg food pellets were delivered individually at 60-sec intervals, independently of behaviour. Water spouts were available to the animals and the intermittent delivery of food induced high levels of adjunctive drinking. The administration of scopolamine (0.125, 0.25, 0.5, 1.0 mg/kg) produced a dose-related attenuation of this drinking. A dose of physostigmine (0.2 mg/kg) was found to slightly reduce levels of drinking but this dose did not consistently modify the action of scopolamine on this behaviour. Tolerance was found to occur to the action of the highest dose of scopolamine (1.0 mg/kg).
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 54 (1977), S. 273-276 
    ISSN: 1432-2072
    Keywords: Adjunctive drinking ; d-Amphetamine ; Self-administration ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the first experiment four food-deprived rats developed high levels of adjunctive water drinking during daily sessions of intermittent food pellet delivery. When the water was removed and a solution of d-amphetamine sulfate (0.01 mg/ml) put in its place, adjunctive drinking was disrupted towards the end of each session although the rats ingested doses of approximately 0.5 mg/kg daily for over 40 sessions. Consumption of the d-amphetamine solution was increased by injections of several doses of α-methyl-p-tyrosine (AMPT). In a second experiment injections of d-amphetamine (0.25, 0.5, 1.0, 2.0 mg/kg) were found to reduce adjunctive water consumption in six rats. It was also found that the actions of the two highest doses of d-amphetamine were reduced by pretreatment with a dose of AMPT (100 mg/kg), which itself slightly reduced levels of drinking. These results suggest that, although adjunctive drinking may be a useful technique for inducing rats to self-administer d-amphetamine, the amount of drug consumed is limited by a direct action of the drug on drinking.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2072
    Keywords: Chlordiazepoxide ; Self-stimulation ; Selfregulated duration ; Response duration ; Reinforcement ; Fixed interval
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were exposed to a fixed-interval 60-s schedule under which responding was maintained by electrical stimulation of the lateral hypothalamus. The duration of stimulation was controlled by the duration of each lever press that initiated reinforcement. The effects of variation in current intensity and administration of several chlordiazepoxide (CDP) doses (2.5–20 mg/kg IP) were investigated. The duration of stimulation was inversely related to current intensity. Administration of CDP resulted in increases in response rate and the durations of reinforced and nonreinforced responses. CDP increased the response duration reliably more with non-reinforced responses than with responses that served to regulate the duration of stimulation. Thus CDP-induced increases in the duration of brain stimulation with the single lever self-regulation procedure may not be attributed to a specific effect of this compound on neural processes underlying reinforcement. The present results indicate the utility of intermittent schedules in establishing the specificity of drug effects on self-regulated duration of brain stimulation in the single-lever condition.
    Type of Medium: Electronic Resource
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