Behavioral characteristics of olanzapine: an atypical neuroleptic  

非经典安定剂奥氮平的行为学特性(英文)

作　　者：傅雨[1] 朱子涛 陈丽娟 俞蕾平 金国章 

机构地区：[1]中国科学院上海药物研究所

出　　处：《Acta Pharmacologica Sinica》2000年第4期43-48,共6页中国药理学报（英文版）

摘　　要：ABM: To assess the atypical neuroleptic properties of a novel antipsychotic agent, olanzapine (Ola). METHODS: The action of Ola on apomorpine (Apo)-induced climbing behavior, 5-hydroxy-dl-tryptophan (5-HTP)-induced head twitch response, oxotremorine-induced tremor, and the conditioned avoidance behavior in mice were observed. The catalepsy of mice induced by Ola was also investigated. The single unit extracellular recording technique was used to compare the spontaneous firing rate changes of dopamine (DA) cells in the ventral tegmental area (VTA, A10) and the substantia nigra pars compact (SNC, A9) in rats after iv Ola. RESULTS: Ola antagonized the climbing behavior (ED50 1.8 mg · kg-1, po), head twitch behavior (ED50 0.3 mg·kg-1, po), and tremor (ED50 5.2 mg·kg-1, po) in mice. In a conditioned avoidance paradigm in mice, Ola inhibited the avoidance response with an ED50 of 2.72 mg·kg-1 (po). However, the catalepsy was not induced by Ola in mice even under a very high dose of 100 mg ·kg-1 (po). Ola selectively increased the firing rate of DA cells in the VTA, but failed to affect that of SNC DA cells. CONCLUSION: Ola distinguished itself from the typical neuroleptic (eg haloperidol, Hal) and took resemblance of the atypical neuroleptic (eg clozapine, Clo) in 3 aspects: 1) the multiple receptor pharmacodynamics involving D1/D2, 5-HT2 and M-ACh receptors; 2) dose-response separation between the block of conditioned avoidance response and catalepsy induction; and 3) the specificity of action sites of firing rates upon acute drugchallenge.目的:评价新型抗精神病药物奥氮平(Ola)的非经典安定剂特性。方法:用细胞外单位放电记录技术分析中脑腹侧被盖区(VTA)和黑质致密区(SNC)多巴胺(DA)神经元自发放电活动。结果:Ola对抗小鼠攀爬行为、头部抽动行为、震颤行为及小鼠的条件回避行为,但在100mg·kg^(-1)的高剂量下仍不能诱发小鼠的僵住症。Ola增加大鼠VTA但不影响SNCDA神经元的放电活动。结论:1)Ola具有D_1/D_2,5-HT_2和M-ACh多种受体的药效学相互作用的特性;2)对抗条件回避行为和诱发僵住症的不同效应有剂量区别;3)急性给药引起细胞放电频率变化的作用部位有特异性。

关 键 词：OLANZAPINE antipsychotic agents DOPAMINE avoidance learning CATALEPSY electrophysi- ology substantia nigra ventral tegmental area 

分 类 号：R9[医药卫生—药学]