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  • 1
    Electronic Resource
    Electronic Resource
    Evidence for the role of serotonin in the inhibition of specific motor responses (1978)
    Springer
    Psychopharmacology 60 (1978), S. 73-79 
    Details
    ISSN: 1432-2072
    Keywords: Serotonin ; Response inhibition ; Raphe nucleus ; P-chlorophenylalanine ; Passive-avoidance learning ; Omission training
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two behavioural paradigms were used to test the effects of serotonin depletion on a specific form of response inhibition. Treatment with both p-chlorophenylalanine (p-CPA) at 200 mg/kg and lesions of the medial raphe nucleus impaired the acquisition of a step-off passive-avoidance response. The experimental design allowed the elimination of alternative interpretations in terms of increased sensitivity to shock and increased responsiveness to stimuli. p-CPA also impaired response inhibition during an omission-training schedule. The results of the three studies support a general role of serotonin in withholding specific instrumental (reinforced) motor actions. The results contrast with those of studies supporting a role of noradrenaline in response inhibition. A tentative conclusion supports Konorski's (1967) suggestion for differentiation of various types of response inhibition that are mediated by different neurochemical systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00429182
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  • 2
    Electronic Resource
    Electronic Resource
    Does conditioned nausea mediate drug-induced conditioned taste aversion? (1982)
    Springer
    Psychopharmacology 78 (1982), S. 277-281 
    Details
    ISSN: 1432-2072
    Keywords: Conditioned taste aversion ; Scopolamine ; Prochlorperazine ; Lithium ; Amphetamine ; Morphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two antiemetic drugs were tested on the expression of taste aversions previously conditioned in rats with lithium, amphetamine or morphine. Neither prochlorperazine nor scopolamine administered prior to testing attenuated established aversions, although both drugs are known to have antiemetic effects in other species. Negative findings were obtained with a range of doses of prochlorperazine and scopolamine, with strong and weak aversions, with one- and two-stimulus tests, in a repeated one-stimulus extinction procedure, with between- and within-group designs and with hooded, albino, male and female rats. The results do not support the widely accepted hypothesis that conditioned nausea mediates conditioned taste aversion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428165
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  • 3
    Electronic Resource
    Electronic Resource
    An analysis of behavioural mechanisms involved in the acquisition of amphetamine anorectic tolerance (1983)
    Springer
    Psychopharmacology 79 (1983), S. 58-66 
    Details
    ISSN: 1432-2072
    Keywords: Amphetamine anorexia ; Behavioural tolerance ; Food deprivation ; Conditioned taste aversion ; Operant/classical conditioning ; Behavioural augmentation of tolerance ; Compensatory conditioning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Deprived rats given 2.5 mg/kg d-amphetamine before milk access developed anorectic tolerance. Rats given identical treatment after milk access did not exhibit tolerance in a subsequent test when the drug was given before milk access, nor did they subsequently acquire tolerance more rapidly than drug-naive animals. Manipulations of the amount of lab chow given to supplement milk intake did not affect the rate of development of tolerance, indicating that development of anorectic tolerance could not be explained in terms of increasing food deprivation or body weight loss as has often been suggested. The lack of tolerance in subjects drugged chronically after milk intake was shown not to be due to the development of a conditioned taste aversion in these animals. The possibility that tolerance was due to the acquisition of a classically conditioned compensatory response which attenuated drug effects was investigated. In one experiment the injection procedure was used as a potential conditioned stimulus. A series of placebo injections was given to tolerant rats in an attempt to extinguish any conditioned response, but this failed to attenuate tolerance. No compensatory hyperphagic response was seen after placebo injections. A further experiment was performed in which cues accompanying drug administration were made more salient by transferring animals to a distinct environment (noise, odour, light) after drug administration. Giving the drug subsequently in the home environment did not lead to the loss of tolerance predicted by the conditioning model, nor was there any evidence of hyperphagia in response to a placebo injection in the distinct environment. These results offer indirect support for a learning interpretation of amphetamine anorectic tolerance, but not one that involves classical conditioning of a compensatory response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00433017
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  • 4
    Electronic Resource
    Electronic Resource
    The puzzle of drug-induced conditioned taste aversion: Comparative studies with cathinone and amphetamine (1985)
    Springer
    Psychopharmacology 87 (1985), S. 328-333 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432716
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  • 5
    Electronic Resource
    Electronic Resource
    Analysis of the role of drug-predictive environmental stimuli in tolerance to the hypothermic effects of the benzodiazepine midazolam (1986)
    Springer
    Psychopharmacology 90 (1986), S. 513-521 
    Details
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Midazolam ; Tolerance ; Classical conditioning ; Rats ; Body temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of classical conditioning processes in the development of tolerance to the hypothermic effects of the short-acting benzodiazepine midazolam was studied in three experiments in rats. The experiments were all designed so that one set of environmental stimuli reliably predicted drug treatments whilst another set of stimuli predicted control (vehicle) treatment. According to the classical conditioning account of tolerance, the degree of tolerance observed should be greater in the presence of drug-predictive stimuli than in their absence, i.e. tolerance should show environmental (context) specificity. A preliminary study was conducted to determine the dose- and time-effect curves for midazolam-induced hypothermia. The results of this study provided essential background data for the design of all the subsequent tolerance studies. In the first tolerance study, it was found that virtually complete tolerance developed to the hypothermic effects of 4 mg/kg (IP) midazolam given on alternate days. However, the observed tolerance was clearly not environmentally specific. Since there is evidence that conditioned tolerance to some drug effects develops most readily if drugs are given at low doses with long inter-injection intervals, a second study was conducted with a lower (1.6 mg/kg IP) dose of midazolam, which was given every 5th day. Despite these procedural changes, the second study indicated that the observed tolerance again did not show context specificity, even though tolerance developed rapidly with the lower dose of a short acting drug which was given infrequently. In a final study, the experimental procedure was changed again so that the environmental stimuli which predicted drug treatment were only present during the onset of drug-induced hypothermia, in contrast to the procedure adopted in the two previous studies in which the drug-predictive stimuli were present during the onset and the offset of the drug's hypothermic effect. This procedural change was introduced because it was considered possible that the presence of stimuli associated with recovery from the drug's effects might have prevented the development of conditioned tolerance in the first two studies. However, no evidence was obtained for context specific tolerance, even after this further procedural manipulation. These data indicate clearly that it is difficult to demonstrate context specificity of midazolam hypothermic tolerance. A number of possible reasons for these results are considered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174071
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of the CCKB antagonist L-365, 260 on benzodiazepine withdrawal-induced hypophagia in rats (1995)
    Springer
    Psychopharmacology 118 (1995), S. 57-64 
    Details
    ISSN: 1432-2072
    Keywords: CCKB antagonists ; L-365, 260 Benzodiazepines ; Chlordiazepoxide ; Withdrawal Anxiety ; Food Intake ; Hypophagia ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of the selective CCKB antagonist L-365, 260 on chlordiazepoxide (CDP) withdrawal-induced hypophagia was assessed in two related studies in rats pretreated for 21 days with CDP at doses escalated from 10 to 30 mg/kg per day (b.i.d.). L-365, 260 was studied at doses from 0.001 to 10 mg/kg (b.i.d.). There was no evidence that L-365, 260 at any dose alleviated CDP withdrawal-induced hypophagia. These data contrast with reports that CCKB antagonists alleviate behavioural benzodiazepine (BZ) withdrawal symptoms considered to be indicative of “anxiogenesis”. Presumably, such positive effects of CCKB antagonists are due to “functional antagonism”, with enhanced anxiety during BZ withdrawal being attenuated by anxiolytic actions of CCKB antagonists. Collectively, studies with CCKB antagonists and other agents involving a number of different BZ withdrawal signs suggest that BZ withdrawal is a heterogeneous syndrome, with various different underlying mechanisms. CCKB antagonists appear to alleviate only a subset of possible BZ withdrawal signs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245250
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  • 7
    Electronic Resource
    Electronic Resource
    Time sampling of rat exploratory behaviour: A reliable screening test for the C.N.S. effects of anorexic agents (1974)
    Springer
    Psychopharmacology 35 (1974), S. 1-12 
    Details
    ISSN: 1432-2072
    Keywords: Anorexiants ; Activity Analysis ; Time Sampling ; Screening Tests ; Phenylethylamines ; Serotonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of eight experiments were conducted on the acute effects of a number of anorexic agents on rat exploratory behaviour, as assessed by a “time sampling” procedure of behavioural categorisation. Compounds studied were of three types. Firstly, some well known anorexiants (Amphetamine, Diethylpropion, Fenfluramine); secondly, a series of fenfluramine derivatives (Norfenfluramine, SE 780, SE 1513 and SKF 1-39728); and thirdly, an indole derivative (U 22-394A). All the compounds except the latter are based upon a phenylethylamine configuration. The results indicate that amphetamine and diethylpropion are stimulants whilst fenfluramine is a sedative, in accord with the clinical reports of the effects of acute administration of these compounds. All the other phenylethylamines and U 22-394A were found to be sedatives. The technique of activity analysis described here is a useful screening test for psychotropic agents which affect C.N.S. excitability in humans, which is probably superior to other measures of activity in its predictive value. However, it is noted that the effects of acute administration do not always provide a reliable index of chronic effects. The compounds SE 780 and SKF 1-39728 would seem to merit further study. It is suggested that all the fenfluramine derivatives, except SKF 1-39728, have a similar mode of anorexic action to U 22-394A.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00421560
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