PMID: 9551772Apr 29, 1998Paper

Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum

Psychopharmacology
X M LiF P Bymaster

Abstract

The in vivo effects of olanzapine on the extracellular monoamine levels in rat prefrontal cortex (Pfc), nucleus accumbens (Acb) and striatum (Cpu) were investigated by means of microdialysis. Sequential doses of olanzapine at 0.5, 3 and 10 mg/kg (s.c.) dose-dependently increased the extracellular dopamine (DA) and norepinephrine (NE) levels in all three brain areas. The increases appeared 30 min after olanzapine administration, 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 Pfc (421% +/- 46 of the baseline) was significantly larger than those in the Acb (287% +/- 24) and Cpu (278% +/- 28). Similarly, the highest NE increase in the Pfc (414% +/- 40) induced by 10 mg/kg olanzapine was larger than those in the Acb (233% +/- 39) and Cpu (223% +/- 24). The DA and NE increases in the Pfc induced by olanzapine at 3 and 10 mg/kg (s.c.) were slightly larger than those induced by clozapine at the same doses. In contrast, haloperidol (0.5 and 2 mg/kg, s.c.) did not change Pfc DA and NE levels. Extracellular levels of a DA metabolite, DOPAC, and tissue concentrations of a released DA metabol...Continue Reading

Citations

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