γ-氨基丁酸对大鼠吗啡戒断症状的影响及其作用机理

目的研究γ-氨基丁酸(GABA)对大鼠吗啡戒断症状的影响及其可能的机理。方法建立大鼠吗啡依赖模型,在戒断症状高峰出现前30min侧脑室(icv)注入GABA或生理盐水(0.9%),观察其戒断症状的改变。用分光光度法测定戒断时大鼠血清及脑组织中一氧化氮(NO)含量、一氧化氮合酶(NOS)活性。结果GABA可缓解吗啡戒断时理毛、湿抖、扭体、咬牙、舔阴等运动反应,减少活动次数,抑制植物神经系统症状。Icv注入10μl(500μg·10μl-1)的GABA可抑制吗啡依赖大鼠血清及脑组织NO含量和血清中NOS活性的增高(P<0.05)。结论GABA可缓解大鼠吗啡戒断症状,其作用机理可能与阿片受体、中枢神经系统中NO的表达机制有关。

EFFECTS OF F -AMINOBUTYRIC ACID ON MORPHINE WITHDRAWAL SYMPTOMS IN RATS AND ITS POSSIBLE MECHANISM

Objective:To study the effects of γ-aminobutyric acid on morphine withdrawal symptoms in rats and its possible mechanism. Methods:Morphine-dependent rats were induced by subcutaneous injection of morphine in gradually increasing doses. GABA 10 μl (500 μg·10 μl -1 )or saline (0.9%) were administered intracerebroventricularly (icv) to the morphine dependent rats 30 min before peak incidence of morphine withdrawal symptoms displayed and then to observe its changes. Nitric oxide synthase(NOS)activity and nitric oxide(NO)output were assessed with spectrophotometric analysis. Results:GABA can significantly attenuate withdrawal behaviors such as grooming,wet dog shakes, writhing,teeth gnashing and cunnilingus movements,and can effectively inhibit autonomic hyperactivity. Levels of NOS activity,NO output in serum,brain tissue around NAc were increased significantly during the period of morphine withdrawal compared with the saline group(P<0.05), while GABA(icv)could inhibit the enhancement of NOS activity, NO output in morphine abstinence session(P<0.05). Conclusion: GABA can decrease the incidence of morphine withdrawal behavior. GABA action of antagonizing drug-dependence may be correlated with the opioid receptors,which can reduce the expression of NO in CNS.