ELECTROPHYSIOLOGICAL EFFECTS OF OLANZAPINE, A NOVEL ATYPICAL ANTIPSYCHOTIC, ON A9 AND A10 DOPAMINE NEURONS

This study examined the effects of the novel atypical antipsychotic ol anzapine (LY170053) on the activity of substantia nigra pars compacta (A9) and ventral tegmental area (A10) dopamine cells in anesthetized r ats. Acute administration of olanzapine (10, 20 mg/kg sc) increased th e number of spontaneously active A10, but not A9, dopamine cells. Chro nic administration of olanzapine (10, 20 mg/kg/day x 21 days) decrease d the number of spontaneously active A10, but not A9, dopamine cells. Administration of the dopamine agonist apomorphine reversed the effect s of chronic olanzapine on A10 cells, indicating a possible depolariza tion-inactivation mechanism. In conclusion, olanzapine has selective e ffects on A10 versus A9 dopamine cells following acute and chronic adm inistration. These effects of olanzapine on dopamine cells are similar to the effects observed with clozapine and may play an important role in the atypical antipsychotic profile of olanzapine.