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Effects of clozapine on behavioral sensitization induced by cocaine

Cited 12 time in Web of Science Cited 12 time in Scopus
Authors
Park, Hye-Jean; Cui, Feng Ji; Hwang, Jae Yeon; Kang, Ung Gu
Issue Date
2010-01
Publisher
ELSEVIER IRELAND LTD
Citation
PSYCHIATRY RESEARCH; Vol.175 1-2; 165-170
Keywords
AKTCocaineCyclic AMP response element binding proteinClozapineBehavioral sensitizationERKPrefrontal cortexPsychosisGlycogen synthase kinase-3
Abstract
Using cocaine-sensitized mice as a model for psychosis. this study investigated whether subchronic treatment with clozapine could affect the sensitized state of the animals and examined the accompanying molecular changes in the brain. To induce sensitization, ICR mice (n = 44) were treated with cocaine for 5 days. After 7 days of withdrawal, sensitization was confirmed by a cocaine challenge. Then. the sensitized animals were treated with clozapine for 5 days and rechallenged with cocaine. The frontal cortices were removed from the mice (n = 16) 24 h after the last challenge, and the phosphorylation status of some key signaling molecules was investigated. Compared with the sensitized mice receiving the vehicle treatment, the sensitized mice receiving subchronic clozapine showed less locomotor activity, with an activity level similar to that of non-sensitized mice. However, clozapine did not directly affect the stimulatory effect of cocaine. Clozapine also reversed some of the sensitization-induced biochemical changes, including increased phosphorylation of GSK-3 beta and CREB, in the frontal cortex. Subchronic treatment with clozapine apparently de-sensitized the sensitized mice. The long-term effect of clozapine on stimulant-induced sensitization may be related to the therapeutic effect of the drug as an antipsychotic agent. Crown Copyright (C) 2008 Published by Elsevier Ltd. All fights reserved.
ISSN
0165-1781
Language
English
URI
http://hdl.handle.net/10371/78522
DOI
https://doi.org/10.1016/j.psychres.2008.10.005
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College of Medicine/School of Medicine (의과대학/대학원)Psychiatry (정신과학전공)Journal Papers (저널논문_정신과학전공)
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