不同剂量吗啡(起始剂量6, 12mg/kg)以20%递增给药10天致瘾。在偏倚的三箱式实验箱中，以纳络酮( 0.5, 1 mg/kg)与起始偏爱侧结合，使大鼠对实验箱两侧的选择性发生改变。结果表明:
分别在纳络酮条件化训练前，杏仁中央核内给予多巴胺D1激动剂SKF38393 (1, 3Ng/}I), D1受体拮抗剂SCH23390(1, 3ug/uI), D2和D3受体的混合激动剂喳毗罗(1, 3Ng/闭)和D2拮抗剂雷氯必利(1, 4ug/ul)，考察多巴胺受体不同亚型对阿片戒断地负性情绪获得的影响。结果表明:
6. SKF38393激动杏仁中央核D1受体对阿片戒断诱发的条件性厌恶反应没有影响;而1、3ug/NI SCH23390阻滞D1受体，呈现剂量依赖性的抑制条件性位置厌恶反应的获得。
The negative affective state of opiate abstinence plays an important role in craving and relapse to compulsive drug use. Dopamine pathway is critically involved in both the rewarding properties of opiate drugs and the aversive effects of opiate withdrawal. The amygdala is a crucial component of the neuronal circuitry mediating emotional associative learning. Dopamine terminals in the amygdala are distributed primarily in the central nucleus of the amygdala (CeA).
To establish the model of conditioned place aversion (CPA) of morphine-treated rat, this study used different visual and tactual cues in the place conditioning apparatus as the conditioned stimulus (CS) and an injection of naloxone as the unconditioned stimulus (UCS). The CS was paired with UCS twice. The distinct CPA was induced in morphine dependence rat. 6-OHDA lesion method and Intracerebral drug microinjecting technique was used to assess the effect of dopamine system of CeA on the acquisition of CPA in morphine dependent rats.
The main results are the following:
Rats were made physically dependence with the initiative dose (6 mg/kg) of morphine by intraperitoneal injection in 20% increased every day within 10 days and were trained to develop CPA induced by naloxone (0.5 or 1.0 mg/kg) in a biased three-compartment conditioned place apparatus. The results showed that morphine-dependent rats with naloxone treatment produced distinct CPA. Though the effects of both high- and low-dose naloxone on the acquisition of CPA had no significant difference in dependent-rats, the conditional training with the low-dose naloxone induced more long-lasting CPA ,than that with high-dose. The place aversion was also induced by high-dose naloxone in naive rat, but lasted transiently. The conditional training with high- or low- dose naloxone produced CPA in the dependent rats, but not, in the abstinent rats.
The acquisition of CPA in morphine dependence was impaired by bilateral microinjection 6-OHDA to CeA.
To examine the role of CeA DA D1，D2 receptor in the acqusition of CPA in morphine dependence, the DA D1 agonist, SKF38393 (1，3Ng/NI), D1 antagonist, SCH23390 (1，3Ng/NI), D2/D3 agonist, quinpirole (1，3Ng/NI), D2 antagonist, raclopride (1，4Ng/NI) was infused into CeA prior naloxone conditioning. Pre-conditioning infusions of SCH23390 dose-dependently attenuated the acquisition of CPA. And intra-CeA administration of low-dose quinpirole (1 Ng/NI) abolished the CPA, but not high-dose (1 Ng/NI).
In conclusion, dopamine system of CeA was involved in the negative affective components of morphine abstinence. And dopamine D1 receptor and D2 receptor within the CeA contributes to the acquisition of aversive emotion of opiate withdrawal.