Sensitization of Ventral Tegmental Area Dopamine Neurons to the Stimulating Effects of Ethanol
Sensitization of Ventral Tegmental Area Dopamine Neurons to the Stimulating Effects of Ethanol
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DOI：
10.1111/j.1530-0277.2009.00985.x
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发表时间：
2009-09-01
影响因子：
3.2
通讯作者：
McBride, William J.
中科院分区：
文献类型：
--
作者：
Ding, Zheng-Ming;Rodd, Zachary A.;McBride, William J.
背景：以往的研究表明，长期饮酒增加了后腹侧被盖区（p-VTA）对乙醇强化效应的敏感性。目前的研究测试的假设，即局部暴露的p-VTA的乙醇会增加多巴胺（DA）神经元的敏感性，以刺激efficaciousness of ethanol.Methods：实验1研究乙醇的刺激作用后，在p-VTA的p-VTA的乙醇预处理7天。将200 mg%乙醇或人工脑脊液（aCSF）微量注射入成年雌性Wistar大鼠的p-VTA中，每天一次，持续7天。在第8天，大鼠接受乙醇（100，200，或300毫克%）或aCSF到p-VTA的挑战注射，和细胞外DA水平的测定，在脑桥核（NAc）壳微透析。实验2研究了乙醇（200 mg %）预处理3或5天后对p-VTA的刺激作用。实验3研究的刺激效果的乙醇（200毫克%）7天后的最后7天的乙醇（200毫克%）预处理的p-VTA.Results：实验1：在aCSF和乙醇预处理大鼠，挑战微量注射乙醇剂量依赖性增加DA释放的NAC壳，乙醇预处理组显着增加。实验2：5天而不是3天的乙醇预处理方案增加了p-VTA多巴胺神经元对乙醇攻击的反应。实验三：结论：反复暴露于p-VTA可使投射至NAc壳的DA能神经元产生神经适应性改变，使这些神经元对乙醇刺激的敏感性持续增加。
Background:Previous studies indicated that chronic alcohol drinking increased the sensitivity of the posterior ventral tegmental area (p-VTA) to the reinforcing effects of ethanol. The current study tested the hypothesis that local exposure of the p-VTA to ethanol would increase the sensitivity of dopamine (DA) neurons to the stimulating effects of ethanol.Methods:Experiment 1 examined the stimulating effects of ethanol in the p-VTA after a 7-day ethanol pretreatment in the p-VTA. Adult female Wistar rats were pretreated with microinjections of 200 mg% ethanol or artificial cerebrospinal fluid (aCSF) into the p-VTA once a day for 7 days. On the eighth day, rats received a challenge injection of ethanol (100, 200, or 300 mg%) or aCSF into the p-VTA, and extracellular DA levels were measured in the nucleus accumbens (NAc) shell with microdialysis. Experiment 2 examined the stimulating effects of ethanol (200 mg%) after a 3- or 5-day ethanol (200 mg%) pretreatment in the p-VTA. Experiment 3 examined the stimulating effects of ethanol (200 mg%) 7 days after the last of the 7-day ethanol (200 mg%) pretreatments in the p-VTA.Results:Experiment 1: in both aCSF- and ethanol-pretreated rats, the challenge microinjection of ethanol dose-dependently increased DA release in the NAc shell, with significantly greater increases in ethanol-pretreated groups. Experiment 2: the 5-day, but not 3-day, ethanol pretreatment protocol increased the response of p-VTA dopamine neurons to the ethanol challenge. Experiment 3: the increased stimulating effects of ethanol were still evident after 7 days.Conclusions:The results indicate that repeated local ethanol exposure of the p-VTA produced neuroadaptations in DA neurons projecting to the NAc shell, resulting in a persistent increase in the sensitivity of these neurons to the stimulating effects of ethanol.