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  • 1
    Electronic Resource
    Electronic Resource
    Clozapine as a drug of dependence (1999)
    Springer
    Psychopharmacology 142 (1999), S. 369-374 
    Details
    ISSN: 1432-2072
    Keywords: Key words Clozapine ; Withdrawal ; Dependence ; Temperature ; Atypical antipsychotic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: In schizophrenics, clozapine has been reported to induce various withdrawal signs and rapid onset relapse to psychosis on cessation of chronic treatment. Objective: The study was designed to develop an animal model of one aspect of clozapine tolerance and withdrawal using core body temperature measures. Methods: Two groups of 15 female Wistar rats were treated chronically (b.i.d.) with clozapine at 6 or 12 mg/kg per injection for 21 days prior to cessation of drug treatment, withdrawal being studied over 4 consecutive days. Body temperatures were assessed daily throughout the study. Results: Acutely, clozapine induced dose-related hypothermia, to which complete tolerance developed in both groups, the development of tolerance being more rapid in the group treated with 6 mg/kg per injection of clozapine. During withdrawal only the group treated chronically with 12 mg/kg per injection of clozapine showed rapid onset significant hyperthermia. This dissipated progressively over days, and was completely absent after 4 days of withdrawal. Conclusions: Clozapine induced a clear somatic withdrawal sign after chronic treatment. It is suggested that, in future research in both humans and animals, it is important to attempt to differentiate between clozapine withdrawal and clozapine withdrawal-induced relapse to psychosis. It is also important to characterise the clozapine withdrawal syndrome fully in animals; to establish the neurochemical mechanisms involved in such withdrawal; and to determine which novel antipsychotics are most efficacious in inducing clozapine-like withdrawal effects, in suppressing clozapine withdrawal, and in preventing relapse to psychosis in patients being transferred from clozapine to novel atypical antipsychotic drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050901
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  • 2
    Electronic Resource
    Electronic Resource
    Dopamine ligands and the stimulus effects of amphetamine: animal models versus human laboratory data (1997)
    Springer
    Psychopharmacology 130 (1997), S. 2-13 
    Details
    ISSN: 1432-2072
    Keywords: Key words Amphetamine ; Dopamine ; Mechanisms ; Animal models ; Human subjects ; Cocaine ; Drug abuse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Studies with laboratory animals have consistently demonstrated a role for dopamine in mediating the discriminative stimulus (i.e., interoceptive) effects of amphetamine. For example, D2 dopamine agonists mimic the discriminative stimulus effects of amphetamine and D1 and D2 dopamine antagonists generally block them. The discriminative stimulus effects of drugs in animals are believed to parallel their subjective effects in humans. Therefore, it is often assumed that dopamine plays a role in amphetamine-induced subjective effects in humans and it would be reasonable to expect that dopamine antagonists would block the subjective effects of amphetamine. Few studies have tested this hypothesis directly, and those that have have yielded inconsistent results. This paper will review data regarding the effects of dopamine agonists and antagonists on the discriminative stimulus effects of amphetamine in animals and its subjective effects in humans. Possible explanations for the discrepancies between animal and human data will be discussed, and classical assumptions underlying the use of animal models of drug effects will be examined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050207
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of the 5-HT3 antagonist ondansetron on benzodiazepine-induced operant behavioural dependence in rats (1992)
    Springer
    Psychopharmacology 109 (1992), S. 461-465 
    Details
    ISSN: 1432-2072
    Keywords: Operant behavioural dependence ; 5-HT3 antagonists ; Ondansetron ; Withdrawal ; Benzodiazepines ; Chlordiazepoxide ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was designed to assess whether rats made tolerant to the suppressant action on Fixed Ratio operant responding of the benzodiazepine (BZ) chlordiazepoxide (CDP) would show behavioural disruption on drug withdrawal—so-called operant behavioural dependence. In addition, the study examined the effects of the 5-HT3 antagonist ondansetron on such operant behavioural dependence. During 42 consecutive days of CDP treatment, at deses escalated from 10 to 30 mg/kg/day, marked tolerance developed to the rate-suppressant action of CDP. On subsequent days, during spontaneous withdrawal, response rates declined significantly by around 30% in animals treated with saline, although some recovery of responding was seen over successive days of withdrawal. Similar reductions in responding followed by recovery were seen in rats treated with the 5-HT3 antagonist ondansetron (0.01–0.1 mg/kg, b.i.d.). These findings demonstrate for the first time that it is possible to use operant procedures to detect spontaneous BZ withdrawal. They also suggest, in agreement with recent studies from this laboratory (Leathley and Goudie 1992), that 5-HT3 antagonists may have relatively limited utility in treating some signs of BZ dependence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247724
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    Paper (German National Licenses)
    Fulltext
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