Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors.
Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors.
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DOI：
10.1016/j.neuroscience.2016.07.006
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发表时间：
2016-10-01
期刊：
影响因子：
3.3
通讯作者：
Budygin EA
中科院分区：
文献类型：
--
作者：
Mikhailova MA;Bass CE;Grinevich VP;Chappell AM;Deal AL;Bonin KD;Weiner JL;Gainetdinov RR;Budygin EA
最近的光遗传学研究表明，伏隔核多巴胺的时相释放可能在自然行为和药物奖赏相关行为的多个方面起到因果作用。强直性多巴胺释放在奖赏消耗性行为中的作用尚不清楚。本研究采用组合病毒介导的基因传递方法，在大鼠中脑边缘多巴胺神经元上表达ChR2。我们使用光学激活这个多巴胺回路来模拟伏隔核多巴胺的强直释放，并探索腹侧被盖区(VTA)-伏核投射中这种形式的多巴胺信号与自然奖赏的消耗之间的因果关系。使用两瓶选择范式(蔗糖和水)，实验表明，对中脑边缘多巴胺传递的紧张性光遗传刺激显著减少了奖励消耗行为。具体地说，在饮酒过程中，痛饮次数、舔舔次数和蔗糖量显著减少。值得注意的是，伏核中VTA多巴胺胞体或多巴胺终末的激活会导致相同的行为后果。在相同的实验条件下，摄水量没有明显的变化。总而言之，这些数据表明，对伏隔核多巴胺释放的紧张性光遗传刺激足以抑制奖赏成瘾行为，可能是通过阻止该回路参与被认为是基于奖赏的行为所必需的阶段活动。
Recent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats. We used optical activation of this dopamine circuit to mimic tonic dopamine release in the nucleus accumbens and to explore the causal relationship between this form of dopamine signaling within the ventral tegmental area (VTA)-nucleus accumbens projection and consumption of a natural reward. Using a two bottle choice paradigm (sucrose vs. water), the experiments revealed that tonic optogenetic stimulation of mesolimbic dopamine transmission significantly decreased reward consummatory behaviors. Specifically, there was a significant decrease in the number of bouts, licks and amount of sucrose obtained during the drinking session. Notably, activation of VTA dopamine cell bodies or dopamine terminals in the nucleus accumbens resulted in identical behavioral consequences. No changes in the water intake were evident under the same experimental conditions. Collectively, these data demonstrate that tonic optogenetic stimulation of VTA-nucleus accumbens dopamine release is sufficient to inhibit reward consummatory behavior, possibly by preventing this circuit from engaging in phasic activity that is thought to be essential for reward-based behaviors.