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Effects Of Acute And Long‐Term Typical Or Atypical Neuroleptics On Morphine‐Induced Behavioural Effects In Mice

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Clinical and Experimental Pharmacology and Physiology

Published online on

Abstract

It has been suggested that the high prevalence of drug abuse in schizophrenics is related to chronic treatment with typical neuroleptics and dopaminergic supersensitivity that develops as a consequence. Within this context, atypical neuroleptics do not seem to induce this phenomenon. We investigated the effects of acute administration or withdrawal from long‐term administration of haloperidol and/or ziprasidone on morphine‐induced open‐field behaviour in mice. In the first experiment, mice received an injection of haloperidol (1 mg/kg) or several doses of ziprasidone (2, 4 or 6 mg/kg) and had their motor activity quantified in the open‐field. The second experiment aimed to verify the effects of an acute injection of haloperidol (1 mg/Kg) or ziprasidone (6 mg/kg) on 20 mg/kg‐morphine‐induced behaviours in the open‐field. In the third experiment, mice were treated with haloperidol and/or ziprasidone for 20 days. After 72 h, animals received an injection of 20 mg/kg morphine and were exposed to the open‐field. Acute haloperidol or ziprasidone decreased spontaneous open‐field general activity and abolished morphine‐induced locomotor stimulation. Withdrawal from haloperidol or ziprasidone did not modify morphine‐elicited behaviours in the open‐field. It is suggested that withdrawal from neuroleptic treatments does not contribute to morphine acute effects in schizophrenic patients. This article is protected by copyright. All rights reserved.