条件性位置厌恶大鼠伏隔核壳区多巴胺及其代谢产物3，4二羟基苯乙酸水平变化

目的探讨伏隔核壳区（AcbSh）多巴胺（DA）及其代谢产物3，4-二羟基苯乙酸（DOPAC）在吗啡依赖戒断所致厌恶动机中的作用，揭示阿片依赖戒断的厌恶动机机制。方法40只SPF级雄性Sprage．Dawley大鼠分为实验组（吗啡＋纳洛酮，MN组）与对照组（吗啡＋生理盐水，MS组；生理盐水＋纳洛酮，sN组），连续6．5d吗啡注射（10mg／kg，bid，IP）一次纳洛酮催瘾（0．3mg／kg，IP），同时搭配条件性位置训练箱建立条件性位置厌恶（CPA）大鼠模型。在立体定位术后3-5d，CPA建立前、后收集AcbSh中的细胞外液，采用高效液相色谱-电化学方法对透析液中DA及DOPAC浓度进行测定。结果连续6．5d的吗啡注射与纳洛酮一次催瘾搭配，实验组大鼠表现出明显的厌恶动机，在伴药侧的时间[（230．01±24．76）S]明显缩短，与实验前[（566．04±19．80）s]相比，差异具有统计学意义（t=11．889，P〈0．01）。CPA建立后，MN组AcbSh中DA水平（1．72±0．10）明显升高，与MS组（0．95±0．05）和sN组（0．09±0．06）相比差异有统计学意义（F=42．319，P〈0．01）；MN组DOPAC水平（1．56±0．07）与MS组（1．19±0．04）、SN组（1．07±0．02）相比，明显升高，差异具有统计学意义（F=25．375，P〈0．01）。结论AcbSh中DA及DOPAC可能参与CPA的建立，中脑边缘系统的多巴胺机制可能在物质依赖厌恶动机中起到十分重要的调节作用。

Accumbal dopamine and its metabolites 3,4 dihydroxyphenylacetic acid activity on conditioned place aver- sion rats

Objective To discuss the role of dopamine（DA） and its metabolites 3,4 dihydroxyphenylace- tic acid （DOPAC） in the shell of aecumbens nucleus on the aversive motivation induced by morphine withdrawl,in order to partly understand the mechanism of the negative reinforcement after opioid withdrawal. Methods 40 male Sprage-Dawley rats were randomly divided into experimental group （morphine ＋ naloxone, MN ） and control group （ morphine ＋ saline, MS ; saline ＋ naloxone, SN ） , and 6.5 days after morphine injection, naloxoue （ 0.3 rag/ kg, IP ） was used for once injection to establish the conditioned place aversion（CPA） rat model.At the time of 3-5 days after the stereotactic surgery, the extracellular fluid was collected by microdialysis, and then detected the con- centration of DA and DOPAC with high performance liquid chromatograph-electrochemical detection （HPLC-EC） before and after CPA establishment.Results The CPA model could be successfully established by continuous mor- phine injection for 6 and half days and once naloxone injection.The rats showed obvious aversive motivation, and the avoidance time to the ualoxone-paired side was shorter than that of non-CPA rats （ （ 230.01 ± 24.76 ） s vs （566.04±19.80）s, t= 11.889, P〈0.01）.Compared with the MS（0.95±0.05） and SN group（0.89±0.06） ,the lev- els of dopamine in MN group（1.72±0.10） significantly increased after the establishment of CPA（F= 42.319, P〈 0.01）.And DOPAC in MN group（1.56±0.07） were higher than MS（1.19±0.04） and SN（1.07±0.02） after CPA established（F=25.375, P〈0.01）.Conclusion DA and DOPAC in the shell of accumbens nucleus may participate in the formation of CPA, and play a important role in the regulation of morphine aversive motivation.