Regional differences in chronic neuroleptic effects on extracellular dopamine activity

The extracellular levels of dopamine (DA) and DA metabolites in the caudate-putamen (CPu) and the nucleus accumbens (NA) of rats following administration of haloperidol (HAL) decanoate and fluphenazine (FLU) decanoate for 8 months were assessed using intracranial microdialysis 1 month after final injection. Both HAL- and FLU-treated animals showed persisting plasma neuroleptic levels at time of sacrifice. Extracellular basal levels of homovanillic acid (HVA) in the CPu were significantly elevated in the FLU-treated animals, while basal levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the CPu were significantly elevated in the HAL-treated animals. Basal levels of DA and the serotonin metabolite, 5-hydroxyindoleacetic acid (5HIAA) in the CPu were not significantly different between groups. No significant between-group differences were found for basal levels of any of the analytes in the NA. Neuroleptic-treated animals showed an enhanced response to direct infusion through the dialysis probe of amphetamine (1 microM) and nomifensine (10 microM) in the CPu but not the NA. These results suggest that chronic neuroleptic treatment produces enhanced extracellular DA activity in nigrostriatal, but not mesolimbic DA pathways.