Crespo Jose A, Sturm Katja, Saria Alois, Zernig Gerald
Division of Neurochemistry, Department of Psychiatry, Medical University Innsbruck, A-6020 Innsbruck, Austria.
J Neurosci. 2006 May 31;26(22):6004-10. doi: 10.1523/JNEUROSCI.4494-05.2006.
Neurotransmitter release in the nucleus accumbens core (NACore) during the acquisition of remifentanil or cocaine reinforcement was determined in an operant runway procedure by simultaneous tandem mass spectrometric analysis of dopamine, acetylcholine, and remifentanil or cocaine itself. Run times for remifentanil or cocaine continually decreased over the five consecutive runs of the experiment. Intra-NACore dopamine, acetylcholine, and drug peaked with each intravenous remifentanil or cocaine self-administration and decreased to pre-run baseline with half-lives of approximately 10 min. As expected, remifentanil or cocaine peaks did not vary between the five runs. Surprisingly, however, drug-contingent dopamine peaks also did not change over the five runs, whereas acetylcholine peaks did. Thus, the acquisition of drug reinforcement was paralleled by a continuous increase in acetylcholine overflow in the NACore, whereas the overflow of dopamine, the expected prime neurotransmitter candidate for conditioning in drug reinforcement, did not increase. Local intra-accumbens administration by reverse microdialysis of either atropine or mecamylamine completely and reversibly blocked the acquisition of remifentanil reinforcement. Our findings suggest that activation of muscarinic and nicotinic acetylcholine receptors in the NACore by acetylcholine volume transmission is necessary during the acquisition phase of drug reinforcement conditioning.
在瑞芬太尼或可卡因强化获取过程中，通过对多巴胺、乙酰胆碱以及瑞芬太尼或可卡因本身进行同步串联质谱分析，在操作性跑道程序中确定伏隔核核心（NACore）中的神经递质释放。在实验的连续五次运行中，瑞芬太尼或可卡因的运行时间持续减少。每次静脉注射瑞芬太尼或可卡因自我给药后，NACore内的多巴胺、乙酰胆碱和药物达到峰值，并在约10分钟的半衰期后降至运行前基线水平。正如预期的那样，瑞芬太尼或可卡因的峰值在五次运行之间没有变化。然而，令人惊讶的是，与药物相关的多巴胺峰值在五次运行中也没有变化，而乙酰胆碱峰值却发生了变化。因此，药物强化的获取与NACore中乙酰胆碱溢出的持续增加并行，而多巴胺（药物强化中预期的主要神经递质候选物）的溢出并未增加。通过反向微透析在伏隔核内局部给予阿托品或美加明可完全且可逆地阻断瑞芬太尼强化的获取。我们的研究结果表明，在药物强化条件作用的获取阶段，乙酰胆碱通过容积传递激活NACore中的毒蕈碱型和烟碱型乙酰胆碱受体是必要的。
