Ethanol directly excites dopaminergic ventral tegmental area reward neurons
Ethanol directly excites dopaminergic ventral tegmental area reward neurons
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DOI：
10.1097/00000374-199911000-00019
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发表时间：
1999-11-01
影响因子：
3.2
通讯作者：
Appel, SB
中科院分区：
文献类型：
--
作者：
Brodie, MS;Pesold, C;Appel, SB
背景：中脑边缘/中皮层多巴胺通路介导乙醇和其他滥用药物如可卡因和阿片类药物的奖赏效应。腹侧被盖区（VTA）的多巴胺能神经元是中脑边缘/中皮层多巴胺通路的起源细胞。乙醇的奖励性质是由于其能够激发腹侧被盖区的多巴胺能细胞体，从而导致丘脑核中多巴胺释放增加。最近的许多论文推测，乙醇兴奋的多巴胺能腹侧被盖区神经元是间接的，无论是乙醇作用于GABA能或其他interneurons，这反过来又调节多巴胺能腹侧被盖区神经元的活性，或乙醇调制的行动的神经递质门控离子通道中的VTA.Methods：腹侧被盖区神经元急性解离和平板上的盖玻片在电生理记录室。这些神经元产生的自发动作电位可以用细胞贴附的散斑记录来测量。解离过程截断了树突树，切断了突触接触并广泛分散了这些神经元。将多巴胺（10-50 nM）和乙醇（20-120 mM）浴涂，并测量它们对点火速率的影响。经过一些实验，平板细胞被固定和处理的酪氨酸羟化酶，在多巴胺synthesis.Results的限速酶的免疫染色：所有的神经元符合电生理标准，以前建立的多巴胺能腹侧被盖区神经元。多巴胺抑制所有测试的腹侧被盖区神经元，表明多巴胺自身受体的存在。通过这些电生理学和药理学标准鉴定为多巴胺能神经元，并进行免疫组织化学处理，酪氨酸羟化酶免疫反应性染色呈阳性。所有急性分离的腹侧被盖区神经元，确定为多巴胺能的电生理，药理学和免疫组织化学标准，强烈兴奋的行为相关浓度的乙醇。乙醇诱导的兴奋是concentrationdependent.Conclusions：这些数据提供了强有力的证据表明，乙醇直接兴奋多巴胺能腹侧被盖区神经元，因为这种兴奋仍然发生在没有输入从周围的神经元。
Background: The mesolimbic/mesocortical dopamine pathway mediates the rewarding effects of ethanol and other drugs of abuse like cocaine and opiates. Dopaminergic neurons of the ventral tegmental area (VTA) are the cells of origin of the mesolimbic/mesocortical dopamine pathway. Ethanol's rewarding properties result from its ability to excite dopaminergic cell bodies in the VTA which results in increased dopamine release in the nucleus accumbens. Many recent papers have speculated that ethanol excitation of dopaminergic VTA neurons is indirect, either that ethanol acts on GABAergic or other interneurons, which in turn modulate the activity of dopaminergic VTA neurons, or that ethanol modulates the action of neurotransmitter-gated ion channels in the VTA.Methods: VTA neurons were acutely dissociated and plated onto a cover slip in an electrophysiological recording chamber. These neurons generated spontaneous action potentials which could be measured with cell attached loose patch recording. The dissociation procedure truncated the dendritic trees, severed synaptic contacts and widely dispersed these neurons. Dopamine (10-50 nM) and ethanol (20-120 mM) were bath applied and their effects on firing rare were measured. After some experiments, plated cells were fixed and processed for immunostaining of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis.Results: All neurons met electrophysiological criteria previously established for dopaminergic VTA neurons. Dopamine inhibited all VTA neurons tested, indicating the presence of dopamine autoreceptors. All neurons identified as dopaminergic by these electrophysiological and pharmacological criteria, and that were processed for immunohistochemistry, stained positive for tyrosine hydroxylase immunoreactivity. All acutely dissociated VTA neurons, identified as dopaminergic by electrophysiological, pharmacological and immunohistochemical criteria, were robustly excited by behaviorally relevant concentrations of ethanol. The ethanol-induced excitation was concentration-dependent.Conclusions: These data provide strong evidence that ethanol directly excites dopaminergic VTA neurons, as this excitation still occurs in the absence of input from surrounding neurons.