Activation of muscarinic and nicotinic acetylcholine receptors in the nucleus accumbens core is necessary for the acquisition of drug reinforcement
Activation of muscarinic and nicotinic acetylcholine receptors in the nucleus accumbens core is necessary for the acquisition of drug reinforcement
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DOI：
10.1523/jneurosci.4494-05.2006
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发表时间：
2006-05-31
影响因子：
5.3
通讯作者：
Zernig, Gerald
中科院分区：
文献类型：
--
作者：
Crespo, Jose A.;Sturm, Katja;Zernig, Gerald
通过对多巴胺、乙酰胆碱、瑞芬太尼或可卡因本身的同时串联质谱分析，确定了在获得瑞芬太尼或可卡因强化的过程中伏隔核(NACore)的神经递质释放。在连续的五次实验中，瑞芬太尼或可卡因的运行时间不断减少。NACore中的多巴胺、乙酰胆碱和药物在每次静脉注射瑞芬太尼或可卡因时达到峰值，并下降到运行前基线，半衰期约为10分钟。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，药物相关的多巴胺峰值在五次运行中也没有改变，而乙酰胆碱的峰值发生了变化。因此，药物强化的获得与NACore中乙酰胆碱溢出的持续增加平行，而多巴胺的溢出并没有增加，多巴胺是药物强化中条件作用的主要神经递质候选。局部伏隔内注射阿托品或甲戊胺可完全可逆地阻断瑞芬太尼的强化作用。我们的发现表明，在药物强化条件作用的获得阶段，通过乙酰胆碱容量传递激活NACore中的毒碱和烟碱型乙酰胆碱受体是必要的。
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 similar to 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.