Pothos E, Rada P, Mark G P, Hoebel B G
Department of Psychology, Princeton University, NJ 08544-1010.
Brain Res. 1991 Dec 6;566(1-2):348-50. doi: 10.1016/0006-8993(91)91724-f.
This study shows the effect of opiate withdrawal on dopamine (DA) in the nucleus accumbens (NAC). Microdialysis was used to detect variations in extracellular DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the NAC of freely moving rats during acute and chronic morphine treatment followed by naloxone-precipitated withdrawal with and without clonidine. Basal levels of extracellular DA did not change between sessions, but morphine (20 mg/kg, i.p.) caused a significant and identical increase in extracellular DA and metabolites in both the acute phase (day 1) and the chronic phase (day 7). On day 8, naloxone (20 mg/kg i.p.) caused a significant decrease in DA levels accompanied by typical withdrawal symptoms such as wet dog shakes and teeth-chattering. Clonidine pretreatment (200 micrograms/kg, i.p.) eliminated both the withdrawal symptoms and the DA decrease. These results support the view that morphine increases extracellular DA at times when the drug is rewarding and also suggest that the converse may be true; morphine withdrawal decreases DA release in association with the aversive state.
本研究显示了阿片类药物戒断对伏隔核（NAC）中多巴胺（DA）的影响。采用微透析技术检测自由活动大鼠在急性和慢性吗啡治疗后，经纳洛酮诱发戒断（有无可乐定）过程中，伏隔核细胞外DA、二羟基苯乙酸（DOPAC）和高香草酸（HVA）的变化。各实验阶段细胞外DA的基础水平无变化，但吗啡（20mg/kg，腹腔注射）在急性期（第1天）和慢性期（第7天）均引起细胞外DA及其代谢产物显著且相同程度的增加。在第8天，纳洛酮（20mg/kg腹腔注射）导致DA水平显著下降，并伴有典型的戒断症状，如湿狗样抖动和牙齿打颤。可乐定预处理（200μg/kg，腹腔注射）消除了戒断症状和DA的下降。这些结果支持了吗啡在产生奖赏作用时会增加细胞外DA的观点，同时也表明反之可能成立；吗啡戒断与厌恶状态相关联，会减少DA的释放。
