Stockton M E, Rasmussen K
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Neuropsychopharmacology. 1996 Feb;14(2):97-105. doi: 10.1016/0893-133X(94)00130-R.
This study examined the effects of the novel atypical antipsychotic olanzapine (LY170053) on the activity of substantia nigra pars compacta (A9) and ventral tegmental area (A10) dopamine cells in anesthetized rats. Acute administration of olanzapine (10, 20 mg/kg sc) increased the number of spontaneously active A10, but not A9, dopamine cells. Chronic administration of olanzapine (10, 20 mg/kg/day x 21 days) decreased the number of spontaneously active A10, but not A9, dopamine cells. Administration of the dopamine agonist apomorphine reversed the effects of chronic olanzapine on A10 cells, indicating a possible depolarization-inactivation mechanism. In conclusion, olanzapine has selective effects on A10 versus A9 dopamine cells following acute and chronic administration. 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.
本研究检测了新型非典型抗精神病药物奥氮平（LY170053）对麻醉大鼠黑质致密部（A9）和腹侧被盖区（A10）多巴胺能细胞活性的影响。急性给予奥氮平（10、20mg/kg，皮下注射）可增加自发活动的A10多巴胺能细胞数量，但对A9多巴胺能细胞无此作用。慢性给予奥氮平（10、20mg/kg/天，共21天）可减少自发活动的A10多巴胺能细胞数量，但对A9多巴胺能细胞无此作用。给予多巴胺激动剂阿扑吗啡可逆转慢性奥氮平对A10细胞的作用，提示可能存在去极化失活机制。总之，急性和慢性给予奥氮平后，其对A10多巴胺能细胞与A9多巴胺能细胞具有选择性作用。奥氮平对多巴胺能细胞的这些作用与氯氮平的作用相似，可能在奥氮平的非典型抗精神病作用中发挥重要作用。
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