Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration.
Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration.
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DOI：
10.3389/fnbeh.2013.00173
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发表时间：
2013
影响因子：
3
通讯作者：
Budygin EA
中科院分区：
文献类型：
--
作者：
Bass CE;Grinevich VP;Gioia D;Day-Brown JD;Bonin KD;Stuber GD;Weiner JL;Budygin EA
有令人信服的证据表明，急性酒精暴露刺激腹侧被盖区(VTA)多巴胺细胞活动，VTA依赖的伏核终末区域的多巴胺释放在酒精饮酒行为的调节中起着不可或缺的作用。不幸的是，由于技术限制，VTA多巴胺细胞激活和乙醇自我给药之间的特定时间动力学尚不清楚。事实上，建立特定的多巴胺传递模式和饮酒行为之间的因果联系已被证明是难以捉摸的。在这里，我们试图利用一种新开发的病毒介导的基因传递策略来解决我们知识中的这些差距，该策略可以选择性地在野生型大鼠VTA的多巴胺细胞上表达通道视紫红质-2(ChR2)。然后，我们使用这种方法来精确控制自愿饮酒期间VTA多巴胺的传递。结果证实ChR2在VTA多巴胺细胞上选择性表达，向VTA传递蓝光脉冲可诱导伏核终末区域多巴胺的释放，具有很高的时间和空间精度。短暂的高频VTA刺激诱导伏隔核多巴胺释放的时相模式。较低频率的刺激，持续时间较长，会模仿伏隔多巴胺的紧张增加。值得注意的是，在间歇性饮酒过程中使用这种光遗传学方法，我们发现对VTA多巴胺细胞的持续刺激而不是相变刺激选择性地减弱了饮酒行为。总之，这些数据证明了一种新的病毒靶向策略的有效性，该策略可以用于将视蛋白的表达限制在标准近交系动物的多巴胺细胞中，并提供了第一个因果证据，证明VTA多巴胺神经元的紧张性激活选择性地减少了乙醇的自我给药行为。
There is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA) dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive. Here, we sought to address these gaps in our knowledge using a newly developed viral-mediated gene delivery strategy to selectively express Channelrhodopsin-2 (ChR2) on dopamine cells in the VTA of wild-type rats. We then used this approach to precisely control VTA dopamine transmission during voluntary ethanol drinking sessions. The results confirmed that ChR2 was selectively expressed on VTA dopamine cells and delivery of blue light pulses to the VTA induced dopamine release in accumbal terminal fields with very high temporal and spatial precision. Brief high frequency VTA stimulation induced phasic patterns of dopamine release in the nucleus accumbens. Lower frequency stimulation, applied for longer periods mimicked tonic increases in accumbal dopamine. Notably, using this optogenetic approach in rats engaged in an intermittent ethanol drinking procedure, we found that tonic, but not phasic, stimulation of VTA dopamine cells selectively attenuated ethanol drinking behaviors. Collectively, these data demonstrate the effectiveness of a novel viral targeting strategy that can be used to restrict opsin expression to dopamine cells in standard outbred animals and provide the first causal evidence demonstrating that tonic activation of VTA dopamine neurons selectively decreases ethanol self-administration behaviors.
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影响因子：
4.7
作者：
Kita, Justin M.;Parker, Lauren E.;Wightman, R. Mark
通讯作者：
Wightman, R. Mark
影响因子：
4.1
作者：
Henderson, Michael B.;Green, Alan I.;Leiter, James C.
通讯作者：
Leiter, James C.
DOI：
10.1111/j.1530-0277.2011.01722.x
发表时间：
2012-07
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Nam HW;McIver SR;Hinton DJ;Thakkar MM;Sari Y;Parkinson FE;Haydon PG;Choi DS
通讯作者：
Choi DS
影响因子：
3.3
作者：
GRACE, AA;BUNNEY, BS
通讯作者：
BUNNEY, BS
影响因子：
3.3
作者：
通讯作者：
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