去甲肾上腺素系统参与苯二氮12的抗焦虑作用

在安定的药物鉴别性刺激抗焦虑模型上,中枢肾上腺素突触前α_2受体激动剂可乐定(10～60μg/kg),不仅可使安定的量效曲线显著左移,而且可使氯氮(艹卓)和Ⅰ型苯二氮(艹卓)受体激动剂CL218872对安定鉴别性刺激泛化的量效曲线显著左移。中枢肾上腺素突触前α_2受体拮抗剂育亨宾可阻断可乐定的这一作用,且使安定量效曲线显著右移。安定鉴别性刺激,可被中枢苯二氮(艹卓)受体拮抗剂Ro15-1788完全阻断,而GABA_A型受体拮抗剂荷包牡丹碱则不能阻断。结果提示,中枢去甲肾上腺素系统参与介导苯二氮(艹卓)抗焦虑作用。

Involvement of central norepinephrine system in the anxiolytic action of benzodiazepines

Effect of clonidine,a pre-synaptic adrenoceptor agonist,on the anxio-lytic action of diazepam was assessed with the diazepam stimulus procedure,a putative an-xiolytic model of benzodiazepines in rats.Clonidine (10-60μg/kg)not ony significantly shifted the dose-effect curve of diazepm stimulus,but also the dose-effect curves generalizing to diazepam stimulus of chlordiazepoxide and CL218872 to the left.The potentiating effects of clonidine on the diazepam stimulus were completely antagonized by yohimbine 50~300μg/kg).Ro15-1788,an antagonist of central benzodiazepinc receptor,antago-nized the diazepam stimulus in a dose-dependent manner.Yohimbine (1.0 mg/kg)sig-nificiantly shifted the dose-effect curve of dia-zepam stimulus to the right.However,bicucul-line,an antagonist of GABAA receptor,did not show significant effect on the diazepam stimulus.Our results suggest that the central norepinephrine system may be involved in the anxiolytic action of benzodiazepines.