Moroi K, Takashi K, Kuga T
Department of Neurophysiology, School of Medicine, Chiba University, Japan.
Jpn J Pharmacol. 1988 Aug;47(4):367-78. doi: 10.1254/jjp.47.367.
Harmine (HA) induces a jumping behavior in rats when the central dopaminergic function has been activated. Possible involvement of the GABAergic systems and the benzodiazepine receptors (BZA-R) in the jumping behavior induced by HA and apomorphine (APO) was investigated. Pretreatment with GABAergic agonists, muscimol (0.05-0.2 mg/kg) and diazepam (0.2-1.0 mg/kg), and antagonists, picrotoxin (0.1-0.5 mg/kg) and bicuculline (0.1-0.5 mg/kg), suppressed the jumping behavior in a dose-dependent manner in rats treated with HA (10 mg/kg) and APO (2 mg/kg). After treatment with 2, 5 or 10 mg/kg of HA in combination with 2 mg/kg of APO, a decrease in 3H-diazepam binding to the brain regional membranes was observed in the corpus striatum (CS) in a dose-dependent manner, but not in the other brain regions. The decrease in the 3H-diazepam binding to the CS membranes was proportional to the increase in the HA levels in the CS, and the HA levels were correlated with the intensity of jumping behavior. Pretreatment with Ro 15-1788, an antagonist of BZA-R, suppressed the jumping behavior induced by HA and APO. These results indicated the involvement of the GABAergic systems in the jumping behavior and suggested that HA induced the jumping behavior partly as a result of interacting with the BZA-R.
当中枢多巴胺能功能被激活时, harmine (HA) 会诱导大鼠出现跳跃行为。研究了γ-氨基丁酸能系统和苯二氮䓬受体 (BZA-R) 可能参与HA和阿扑吗啡 (APO) 诱导的跳跃行为。用γ-氨基丁酸能激动剂蝇蕈醇 (0.05 - 0.2 mg/kg) 和地西泮 (0.2 - 1.0 mg/kg) 以及拮抗剂印防己毒素 (0.1 - 0.5 mg/kg) 和荷包牡丹碱 (0.1 - 0.5 mg/kg) 预处理,可剂量依赖性地抑制用HA (10 mg/kg) 和APO (2 mg/kg) 处理的大鼠的跳跃行为。在用2、5或10 mg/kg的HA与2 mg/kg的APO联合处理后,在纹状体 (CS) 中观察到3H-地西泮与脑区膜结合呈剂量依赖性降低,但在其他脑区未观察到。3H-地西泮与CS膜结合的降低与CS中HA水平的升高成比例,且HA水平与跳跃行为的强度相关。用BZA-R拮抗剂Ro 15 - 1788预处理可抑制HA和APO诱导的跳跃行为。这些结果表明γ-氨基丁酸能系统参与了跳跃行为,并提示HA诱导跳跃行为部分是由于与BZA-R相互作用的结果。