Effects of acute and long-term typical or atypical neuroleptics on morphine-induced behavioural effects in mice

<list list-type="1" id="cep12203-list-0001"> 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. In the present study, 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 were given a single injection of haloperidol (1mg/kg, i.p.) or several doses of ziprasidone (2, 4 or 6mg/kg, i.p.) and motor activity was quantified by the open-field test. The aim of the second experiment was to verify the effects of an acute injection of haloperidol (1mg/kg) or ziprasidone (6mg/kg) on 20mg/kg morphine-induced behaviours in the open-field test. In the third experiment, mice were treated with 1mg/kg haloperidol and/or 2, 4 or 6mg/kg ziprasidone for 20days. Seventy-two hours after the last injection, mice were injected with 20mg/kg, i.p., morphine and then subjected to the open-field test. Acute haloperidol or ziprasidone decreased spontaneous general activity and abolished morphine-induced locomotor stimulation. Withdrawal from haloperidol or ziprasidone did not modify morphine-elicited behaviours in the open-field test. The results suggest that withdrawal from neuroleptic treatments does not contribute to the acute effect of morphine in schizophrenic patients.