Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens

The present study was designed to compare the effects of typical and atypic al antipsychotic drugs on extracellular dopamine (DA) levels in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), using in vivo mic rodialysis with dual probe implantation in awake, freely moving rats. Amper ozide (2 and 10 mg/kg), clozapine (5 and 20 mg/kg), and olanzapine (10 mg/k g), all of which are atypical antipsychotics, produced greater increases in extracellular DA levels in the mPFC than in the NAG. Olanzapine (1 mg/kg), risperidone (0.1 and 1 mg/kg), also an atypical antipsychotic, and S-(-)-s ulpiride (25 mg/kg), a typical antipsychotic, produced comparable increases in extracellular DA levels in the mPFC and the NAG. S-(-)-sulpiride (10 mg /kg) and haloperidol (0.1 and 1 mg/kg), another typical antipsychotic, sign ificantly increased extracellular DA levels in the NAC but not in the mPFC. The effects of the six antipsychotic drugs to increase extracellular DA le vels in the mPFC relative to those in the NAC was positively correlated wit h the difference between their pKi values for serotonin (5-hydroxytryptamin e, 5-HT2A) and DA-D-2 receptors and was inversely correlated to their pKi v alues for D-2 or D-3 receptors, but was not for 5-HT2A receptors alone. The se results are consistent with the hypothesis that the ability of antipsych otic drugs to produce a greater increase in prefrontal compared with NAC ex tracellular DA levels may be related, in part, to weak D-2 and D-3 receptor affinity relative to 5-HT2A receptor antagonism.