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 l ong-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 day s later. Intracranial microdialysis was used to assess changes in stri atal extracellular dopamine concentrations. Animals were tested for ca talepsy response on a horizontal bar test while concurrently collectin g 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 t hat had received fluphenazine on the first trial showed significant se nsitization to the cataleptic effects of fluphenazine at both time poi nts. Pretreatment with vehicle did not result in tolerance to dopamine overflow and there was only minimal evidence of cataleptic sensitizat ion to a subsequent fluphenazine challenge. Although the tolerance to dopamine overflow may only indirectly relate to behavioral sensitizati on, these results support the hypothesis that significant behavioral a nd neurochemical alterations persist for prolonged time periods follow ing single neuroleptic exposure.