OLANZAPINE INCREASES IN-VIVO DOPAMINE AND NOREPINEPHRINE RELEASE IN RAT PREFRONTAL CORTEX, NUCLEUS-ACCUMBENS AND STRIATUM

The in vivo effects of olanzapine on the extracellular monoamine level s in rat prefrontal cortex (Pfc), nucleus accumbens (Acb) and striatum (Cpu) were investigated by means of microdialysis. Sequential doses o f olanzapine at 0.5, 3 and 10 mg/kg (SC) dose-dependently increased th e extracellular dopamine (DA) and norepinephrine (NE) levels in all th ree brain areas. The increases appeared 30 min after olanzapine admini stration, reached peaks around 60-90 min and lasted for at least 2 h. The highest DA increases in the Acb and Cpu were induced by olanzapine at 3 mg/kg but at 10 mg/kg in the Pfc. The peak DA increase in the Pf c (421 % +/- 46 of the baseline) was significantly larger than those i n the Acb (287% +/- 24) and Cpu (278% +/- 28). Similarly, the highest NE increase in the Pfc (414% +/- 40) induced by 10 mg/kg olanzapine wa s larger than those in the Acb (233% +/- 39) and Cpu (223% +/- 24). Th e DA and NE increases in the Pfc induced by olanzapine at 3 and 10 mg/ kg (SC) were slightly larger than those induced by clozapine at the sa me doses. In contrast, haloperidol(0.5 and 2 mg/kg, SC) did not change Pfc DA and NE levels. Extracellular levels of a DA metabolite, DOPAC, and tissue concentrations of a released DA metabolite, 3-methoxytyram ine, were also increased by olanzapine, consistent with enhanced DA re lease. However, olanzapine at the three sequential doses did not alter the extracellular levels of either 5-HT or its metabolite, 5-HIAA, in any of the three brain areas. In conclusion, the present studies demo nstrate that in the case of sequential dosing olanzapine more effectiv ely enhances DA and NE release in the Pfc than in the subcortical area s, which may have an impact on its atypical antipsychotic actions.