the effect of chronic atypical antipsychotic drugs and haloperidol on amphetamineinduced dopamine release in vivo the effect of chronic administration of antipsychotic drugs 21 days in drinking water followed by 3 days drug washout on the damphetamine 10 mgkg scinduced increase in dopamine da release in the striatum and the nucleus accumbens of awake freelymoving rats was investigated with microdialysis chronic administration of haloperidol a typical antipsychotic 05 mgkgday decreased basal extracellular da release in the striatum and the nucleus accumbens but did not affect damphetamineinduced da release in either region in marked contrast chronic administration of three atypical antipsychotic drugs amperozide 2 mgkgday clozapine 10 mgkgday and melperone 2 mgkgday increased basal extracellular da and enhanced damphetamineinduced da release in the striatum in the nucleus accumbens basal extracellular da was decreased by chronic amperozide unchanged by chronic clozapine and increased by chronic melperone most significantly damphetamineinduced da release was inhibited by chronic amperozide or clozapine but unaffected by chronic melperone in this region these results suggest that atypical antipsychotic drugs can alter da release in a region specific manner in particular attenuation of amphetaminelike stimulation of da release with reduced basal da release in the nucleus accumbens could contribute to the antipsychotic action of amperozide which has a very weak affinity for d2 da receptors