Schrater P R, Russo A C, Stanton T L, Newman J R, Rodriguez L M, Beckman A L
Department of Psychology, California State University, Long Beach 90840-0901.
Life Sci. 1993;52(19):1535-45. doi: 10.1016/0024-3205(93)90054-7.
The present study examined the effect of prolonged morphine treatment on striatal dopamine (DA) release and metabolism, during the initial phase of the development of morphine dependence. Sprague-Dawley rats were implanted with chronic guides for microdialysis of the striatum. Morphine (two 75-mg pellets, subcutaneous implant) or placebo was given (12 hr) to pentobarbital anesthetized animals. Following recovery from anesthesia, morphine physical dependence was verified by the naloxone-evoked abstinence syndrome. Morphine produced significant increases in the dialysate level of DA nad its metabolites (DOPAC and HVA) above baseline compared to placebo treatment. HVA levels began to increase immediately following morphine administration, whereas DA and DOPAC levels began to increase after a latency of one and three hr, respectively. Morphine effects on striatal DA metabolism included changes in the metabolic disposition of DA. Increases in HVA concentration accompanied increases in DOPAC concentration up to a threshold value of DOPAC efflux; further increases in DOPAC level were associated with decreases in HVA level. These in vivo data suggest that morphine-induced changes in the regulation of striatal dopaminergic function may be an important component of the development of physical dependence.
本研究在吗啡依赖形成的初始阶段，检测了长期吗啡治疗对纹状体多巴胺（DA）释放及代谢的影响。将慢性微透析引导管植入Sprague-Dawley大鼠的纹状体。给戊巴比妥麻醉的动物皮下植入两个75毫克的吗啡丸（12小时）或安慰剂。麻醉苏醒后，通过纳洛酮诱发的戒断综合征来验证吗啡身体依赖性。与安慰剂治疗相比，吗啡使透析液中DA及其代谢物（DOPAC和HVA）水平显著高于基线。给予吗啡后，HVA水平立即开始升高，而DA和DOPAC水平分别在1小时和3小时的潜伏期后开始升高。吗啡对纹状体DA代谢的影响包括DA代谢处置的变化。HVA浓度的增加伴随着DOPAC浓度的增加，直至DOPAC流出的阈值；DOPAC水平的进一步增加与HVA水平的降低相关。这些体内数据表明，吗啡诱导的纹状体多巴胺能功能调节变化可能是身体依赖性形成的重要组成部分。
