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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 78 (1982), S. 277-281 
    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
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 80 (1983), S. 287-307 
    ISSN: 1432-2072
    Keywords: Tolerance ; Sensitization ; Amphetamine ; Cocaine ; Anorexia ; Stimulant ; Operant conditioning ; Classical conditioning ; Animal studies ; Synaptic mechanisms ; Functional tolerance ; Dispositional tolerance ; Behavioural tolerance ; Reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An hypothesis is presented about the nature of behavioural tolerance in animals to stimulant drugs. It is suggested that, in many behavioural procedures, tolerance is due to behavioural adaptation to those drug effects which cause disruption of ongoing rewarded behaviour. This unitary hypothesis accounts for the available data on tolerance and cross-tolerance to stimulants more effectively than all of the other more conventional explanations which are based upon dispositional or functional concepts, the most common of which are described, evaluated, and found to be inadequate. Furthermore, it is suggested that attempts to explain tolerance in terms of changes in synaptic functioning are subject to very considerable problems of interpretation and that an analysis of behavioural mechanisms may be of greater value in understanding the process of behavioural tolerance. Evidence for the basic behavioural hypothesis is outlined in some detail, and a theoretical justification presented for its major assumptions. Operant studies of chronic stimulant effects on behaviour have often produced very complex patterns of data, considerable differences being reported both between subjects and between studies. A speculative model is presented which attempts to account for this pattern of data in tolerance studies.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    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.
    Type of Medium: Electronic Resource
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  • 4
    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
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 118 (1995), S. 57-64 
    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
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  • 6
    ISSN: 1432-2072
    Keywords: Conditioned Taste Aversions ; Amphetamine ; Fenfluramine ; Tolerance ; Cross-Tolerance ; Drug Abuse ; Animal Models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Conditioned taste aversions (C.T.As) established in rats to 0.1% sodium saccharin by intra-peritoneal injections of dl-fenfluramine hydrochloride (6 mg per kg) or d-amphetamine sulphate (2.0 mg per kg) were found to be significantly attenuated, but not abolished altogether, by chronic pretreatment (over 9 days) with the specific drug. Prior treatment with fenfluramine attenuated the aversive effects of amphetamine, but the converse was found not to be the case. These results are considered to refute the “Unnatural need state” and “Novelty” hypotheses of the effects of prior drug experience on the establishment of C.T.As. An alternative explanation of such effects in terms of tolerance is considered, and the possible relevance of the results to studies of drug abuse in humans discussed.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 53 (1977), S. 97-102 
    ISSN: 1432-2072
    Keywords: Fenfluramine ; Norfenfluramine ; Amphetamine ; Drug discrimination ; Stimulus properties of drugs ; Fixed ratio responding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fenfluramine at a dose of 3.0 mg/kg was found to possess discriminative stimulus properties controlling lever selection by rats in a two-lever operant task. Subjects trained to discriminate the ‘Fenfluramine cue’ failed to generalize to amphetamine in extinction tests at doses between 0.25 and 1.0 mg/kg. Subjects did, however, generalize to the fenfluramine metabolite, norfenfluramine, at a dose of 2.0 mg/kg. These data provide further evidence for a pharmacological difference between fenfluramine and amphetamine, and support the hypothesis that norfenfluramine is an active metabolite of fenfluramine. The relevance of these findings to theoretical and methodological aspects of drug discrimination studies is considered.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 45 (1975), S. 119-123 
    ISSN: 1432-2072
    Keywords: Amphetamine ; Conditioned taste aversion ; Alpha-methyl-p-tyrosine ; Catecholamines ; Drug abuse ; Self administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pretreatment with alpha-methyl-p-tyrosine (AMPT) was found to block a conditioned taste aversion (C.T.A.) induced by injection of d-amphetamine sulphate (2.0 mg/kg per kg, i.p.) immediately after first access to 0.1% sodium saccharin. This finding implicates catecholaminergic systems in the induction of C.T.As by amphetamine, and suggests that the aversive properties of the drug are mediated by neurochemical systems which are similar to, or the same as, those which mediate the stimulant, anorectic and rewarding effects of the drug. The results refute a recent suggestion that the use of AMPT in the study of neurochemical mechanisms involved in drug induced taste aversions is precluded by the ability of AMPT itself to induce a C.T.A.; and illustrate an important distinction between pretreatment and post-treatment in taste aversion studies. The results provide further support for recent suggestions that the study of drug induced C.T.As may be of significance for an understanding of drug abuse.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2072
    Keywords: Fenfluramine ; Norfenfluramine ; Anorexia ; Activity Analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The anorexic and behavioural effects of Norfenfluramine were studied in rats. Two separate experiments were conducted involving administration by intra-peritoneal and sub-cutaneous routes respectively. Behavioural effects were assessed by time sampling categorisation on Days 1 and 14 of a 20 day chronic study and anorexic effects by daily weighing. Norfenfluramine was found to be a potent anorexiant, to which tolerance is established fairly quickly. It was also found to possess sedative properties after acute administration, but marked stimulant properties after 14 days chronic administration. These results are similar to those previously reported in a study of Fenfluramine, although the behavioural effects of Norfenfluramine are more marked. The results implicate Norfenfluramine in the anorexic and behavioural effects of Fenfluramine, and provide indirect confirmation of the suggestion made in an earlier paper that Fenfluramine may have chronic stimulant properties.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2072
    Keywords: Amphetamine ; Fenfluramine ; Stereotypy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioural effects of a range of high doses of D-amphetamine and DL-fenfluramine were investigated in rats. Subjects were observed individually for 1 min in every 5 for a period of an hour. During each observation period the presence of any of 6 behavioural patterns was recorded in an “all or none”; fashion Behaviour patterns recorded included: Rearing, Forward Locomotion, Immobility, Backward Locomotion, Circling and Head Swaying. The last 3 behaviours are considered “Abnormal”; in that they were never observed in saline treated controls. The results indicate that, at the doses used in this study, both compounds induce abnormal behaviours, the latency of onset of which is directly proportional to dose. For both compounds an inverse correlation was found between normal and abnormal behaviours. However, the type of abnormal behaviour observed differed considerably between drugs in that fenfluramine elicited Backward Walking and Circling with no Head Swaying, over the dose range 10–30 mg per kg; whilst the predominant abnormal behaviour elicited by D-amphetamine, over the range 5–20 mg per kg, was Head Swaying. At the highest doses of amphetamine used some Backward Walking was elicited, behaviour which was totally absent at the lower doses. The implications of these results for the concept of “stereotypy”; are discussed, and attention is drawn to an important distinction between abnormal and stereotyped behaviour.
    Type of Medium: Electronic Resource
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