Sánchez-Blázquez P, Garzón J
Instituto Cajal, C.S.I.C., Madrid, Spain.
Life Sci. 1994;55(23):PL445-50. doi: 10.1016/0024-3205(94)90098-1.
The effect of intracerebroventricular (i.c.v.) injection of antibodies directed against alpha subunits of Gi, Gx/z, GO and GS regulatory proteins on morphine dependence was analyzed in mice. Animals were rendered tolerant-dependent by subcutaneous (s.c.) implantation of an oily suspension (10 ml/kg) containing 0.1 g/ml of morphine. After 72 h of chronic morphine, 1 mg/kg s.c. naloxone precipitated the withdrawal syndrome. The anti Gi2 alpha, Gx/z alpha, GO1/2 alpha and GS alpha antibodies given 24 h before starting the chronic morphine treatment, reduced the number of jumps recorded. An effect also produced by pertussis toxin, agent impairing the function of Gi/GO transducer proteins. The antibodies injected 24 h before the naloxone challenge reduced the number of animals presenting the jumping behavior, as well as the average number of jumps. This was observed for antibodies against alpha subunits of Gi, Gx/z and GO1/2 proteins. Thus, i.c.v. injection of anti G alpha antibodies by reducing the function of opioid and non-opioid receptors alleviated the morphine withdrawal syndrome.
分析了向小鼠脑室内(i.c.v.)注射针对Gi、Gx/z、GO和GS调节蛋白α亚基的抗体对吗啡依赖性的影响。通过皮下(s.c.)植入含0.1 g/ml吗啡的油悬液(10 ml/kg)使动物产生耐受性依赖。慢性吗啡处理72小时后,1 mg/kg皮下注射纳洛酮引发戒断综合征。在开始慢性吗啡处理前24小时给予抗Gi2α、Gx/zα、GO1/2α和GSα抗体,可减少记录的跳跃次数。百日咳毒素也产生同样的效果,它是一种损害Gi/GO转导蛋白功能的物质。在纳洛酮激发前24小时注射的抗体减少了出现跳跃行为的动物数量以及平均跳跃次数。针对Gi、Gx/z和GO1/2蛋白α亚基的抗体均观察到这种情况。因此,脑室内注射抗Gα抗体通过降低阿片类和非阿片类受体的功能减轻了吗啡戒断综合征。