Rada Pedro, Hoebel Bartley G
Department of Psychology, Princeton University, Princeton, NJ 08544, USA.
Eur J Pharmacol. 2005 Jan 31;508(1-3):131-8. doi: 10.1016/j.ejphar.2004.12.016. Epub 2005 Jan 12.
Diazepam is a benzodiazepine used in the treatment of anxiety, insomnia and seizures, but with the potential for abuse. Like the other benzodiazepine anxiolytics, diazepam does not increase dopamine in the nucleus accumbens. This raises the question as to which other neurotransmitter systems are involved in diazepam dependence. The goal was to monitor dopamine and acetylcholine simultaneously following acute and chronic diazepam treatment and after flumazenil-induced withdrawal. Rats were prepared with microdialysis probes in the nucleus accumbens and given diazepam (2, 5 and 7.5 mg/kg) acutely and again after chronic treatment. Accumbens dopamine and acetylcholine decreased, with signs of tolerance to the dopamine effect. When these animals were put into the withdrawal state with flumazenil, there was a significant rise in acetylcholine (145%, P<0.001) with a smaller significant rise in dopamine (124%, P<0.01). It is suggested that the increase in acetylcholine release, relative to dopamine, is a neural component of the withdrawal state that is aversive.
地西泮是一种用于治疗焦虑、失眠和癫痫发作的苯二氮䓬类药物，但存在滥用的可能性。与其他苯二氮䓬类抗焦虑药一样，地西泮不会增加伏隔核中的多巴胺。这就引出了一个问题，即地西泮依赖还涉及哪些其他神经递质系统。研究目的是在急性和慢性地西泮治疗后以及氟马西尼诱导戒断后同时监测多巴胺和乙酰胆碱。给大鼠在伏隔核植入微透析探针，急性给予地西泮（2、5和7.5mg/kg），慢性治疗后再次给药。伏隔核中的多巴胺和乙酰胆碱减少，对多巴胺效应出现耐受迹象。当用氟马西尼使这些动物进入戒断状态时，乙酰胆碱显著升高（145%，P<0.001），多巴胺有较小幅度的显著升高（124%，P<0.01）。有人提出，相对于多巴胺而言，乙酰胆碱释放的增加是戒断状态中产生厌恶感的神经组成部分。
