异喹啉类生物碱对海洛因依赖大鼠的戒断症状和一氧化氮及一氧化氮合酶的影响

The Effects of HBA on Withdrawal Symptoms,NO and NOS in the CNS of Heroin-dependent Rats

目的:采用海洛因依赖大鼠模型,探讨异喹啉类生物碱(HBA)对阿片类药物依赖性的防治作用及作用机制。方法:实验分为正常组、模型组、低剂量HBA组、中剂量HBA组、高剂量HBA组和可乐定组。除正常组外均皮下注射海洛因,复制海洛因依赖模型。在复制模型的同时给药,末次给药后用纳洛酮催促,观察大鼠戒断症状和体重变化,测定大鼠中枢神经系统中一氧化氮(NO)含量和一氧化氮合酶(NOS)活力。结果:实验结果表明,与模型组相比,给药组大鼠的戒断症状和体重丧失显著减轻(P<0.05,0.01),与模型组相比,给药组大鼠大脑、脑干、脊髓中的NO含量明显升高(P<0.05,0.01),脑干和脊髓中NOS活力增高(P<0.05,0.01)。结论:HBA可减轻海洛因依赖大鼠的戒断症状,HBA拮抗阿片类药物依赖的作用,可能与阿片受体、中枢神经系统中NO的表达机制有关。

Objective: To investigate the mechanism of action of HBA on opioid-dependence using models of heroin(her)-dependent rats. Methods: All of rats were randomly divided into normal group and groups of her-dependence (heroin was s.c. injected). The prophylactic groups were subjected to low, mild and high doses of HBA and clonidine i.p. injection. Withdrawal intensity and body weight loss were observed following i.p. injection of naloxone. The level of nitric oxide (NO) and the activity of nitric oxide synthetase (NOS) in the CNS of rats were observed. Results:The prophylactic experiment indicated that, compared with model group,the withdrawal intensity and body weight loss of the treated rats significantly decreased (P<0.05 or 0.01). The content of NO increased in the CNS of HBA-treated rats and NOS activity increased in brain stem and spinal cord of HBA-treated rats (P<0.01). Conclusion: HBA could decrease the withdrawal intensity of Her-dependence. HBA action of antagonizing drug-dependence might be correlated with the opioid receptors and the expression of NO in CNS mechanism.