Single preexposure to fluphenazine produces persisting behavioral sensitization accompanied by tolerance to fluphenazine-induced striatal dopamine overflow in rats.

Single, previous exposure to a neuroleptic has been shown to produce long-lasting changes in various measures of behavior and neurochemistry upon subsequent drug exposure. The present study examined the effects of a single preexposure to fluphenazine (0.3 or 1.0 mg/kg) or vehicle on the effects of subsequent fluphenazine administration 15 or 30 days later. Intracranial microdialysis was used to assess changes in striatal extracellular dopamine concentrations. Animals were tested for catalepsy response on a horizontal bar test while concurrently collecting dialysis samples. Previous fluphenazine exposure produced a profound tolerance to the effects of subsequent fluphenazine at day 15 or day 30 on increasing extracellular dopamine levels. In addition, animals that had received fluphenazine on the first trial showed significant sensitization to the cataleptic effects of fluphenazine at both time points. Pretreatment with vehicle did not result in tolerance to dopamine overflow and there was only minimal evidence of cataleptic sensitization to a subsequent fluphenazine challenge. Although the tolerance to dopamine overflow may only indirectly relate to behavioral sensitization, these results support the hypothesis that significant behavioral and neurochemical alterations persist for prolonged time periods following single neuroleptic exposure.