Haloperidol (but not ziprasidone) withdrawal potentiates sensitization to the hyperlocomotor effect of cocaine in mice

Haloperidol (but not ziprasidone) withdrawal potentiates sensitization to the hyperlocomotor effect of cocaine in mice

Author Fukushiro, Daniela Fukue Autor UNIFESP Google Scholar
Carvalho, Rita de Cassia Autor UNIFESP Google Scholar
Ricardo, Victor Proenca Autor UNIFESP Google Scholar
Alvarez, Juliana do Nascimento Autor UNIFESP Google Scholar
Carvalho Ribeiro, Luciana Takahashi Autor UNIFESP Google Scholar
Frussa-Filho, Roberto Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract One important contributing factor in the high prevalence of drug abuse disorders seen among schizophrenic patients seems to be related to chronic treatment with typical neuroleptics. We have previously demonstrated that withdrawal from long-term treatment with the typical neuroleptic haloperidol, but not the atypical neuroleptic ziprasidone, potentiated the hyperlocomotor effect induced by a single cocaine injection and cocaine-induced conditioned place preference in mice. in the present study we investigated whether withdrawal from long-term treatment with these same neuroleptics would also modify cocaine-induced hyperlocomotion sensitization, which has been proposed as an animal model for the intensification of drug craving in cocaine addiction. Swiss male mice were i.p. treated with haloperidol (1.0 mg/kg) or ziprasidone (4.0 mg/kg) for 15 days. Twenty-four hours after the last injection, animals received an i.p. injection of cocaine (10 mg/kg) for 5 consecutive days, being placed after each injection in the open-field apparatus in order to perform a drug-environment conditioning. Seven days after the last drug-environment conditioning procedure, the animals were challenged with an i.p. injection of cocaine (10 mg/kg), placed in the open-field apparatus and had their locomotor activity quantified. Withdrawal from haloperidol (but not ziprasidone) potentiated cocaine-induced behavioral sensitization. These results are suggested to be a consequence of the development of the dopaminergic supersensitivity phenomenon by long-term treatment with the typical compound. Our findings provide additional support for the use of atypical agents like ziprasidone in the treatment of schizophrenic patients with comorbid substance abuse disorder. (C) 2008 Elsevier Inc. All rights reserved.
Keywords cocaine-induced behavioral sensitization
dopaminergic supersensitivity
haloperidol
ziprasidone
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundacao Coordenacao de Aperfeicoamento de Pessoal de Nivel
Date 2008-09-30
Published in Brain Research Bulletin. Oxford: Pergamon-Elsevier B.V., v. 77, n. 2-3, p. 124-128, 2008.
ISSN 0361-9230 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 124-128
Origin http://dx.doi.org/10.1016/j.brainresbull.2008.05.004
Access rights Closed access
Type Article
Web of Science ID WOS:000259552900009
URI http://repositorio.unifesp.br/handle/11600/30910

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