Presynaptic opioid and nicotinic receptor modulation of dopamine overflow in the nucleus accumbens
Presynaptic opioid and nicotinic receptor modulation of dopamine overflow in the nucleus accumbens
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DOI：
10.1523/jneurosci.4275-07.2008
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发表时间：
2008-02-13
影响因子：
5.3
通讯作者：
McGehee, Daniel S.
中科院分区：
文献类型：
--
作者：
Britt, Jonathan P.;McGehee, Daniel S.
行为相关刺激促使中脑多巴胺（DA）神经元从紧张性放电模式转换为爆发性放电模式。类似的爆发活动的变化被认为有助于阿片类药物和尼古丁的成瘾作用。这些药物产生的中脑核DA溢出是其病理作用的关键因素。利用脑片电化学技术，我们探讨了阿片类药物对背侧和腹侧纹状体单棘波和爆发波刺激诱发的DA溢出的影响。在特定的亚区的核延髓，μ-阿片类药物抑制DA溢出引起的单穗刺激，而离开所产生的突发刺激不受影响。这与已发表的烟碱受体阻断或脱敏的作用相似，并且通过阿片受体诱导的胆碱能中间神经元抑制介导。而δ-阿片类药物具有类似的作用，κ-阿片类药物抑制诱发DA溢出整个纹状体的方式，是不能克服高频刺激。
Behaviorally relevant stimuli prompt midbrain dopamine (DA) neurons to switch from tonic to burst firing patterns. Similar shifts to burst activity are thought to contribute to the addictive effects of opiates and nicotine. The nucleus accumbens DA overflow produced by these drugs is a key element in their pathological effects. Using electrochemical techniques in brain slices, we explored the effects of opioids on single-spike and burst stimuli-evoked DA overflow in the dorsal and ventral striatum. In specific subregions of the nucleus accumbens, mu-opioids inhibit DA overflow elicited with single-spike stimuli while leaving that produced by burst stimuli unaffected. This is similar to published effects of nicotinic receptor blockade or desensitization, and is mediated by opioid receptor-induced inhibition of cholinergic interneurons. Whereas delta-opioids have similar effects, kappa-opioids inhibit evoked DA overflow throughout the striatum in a manner that is not overcome with high-frequency stimuli.