Acute and chronic ethanol modulate dopamine D2-subtype receptor responses in ventral tegmental area GABA neurons.
Acute and chronic ethanol modulate dopamine D2-subtype receptor responses in ventral tegmental area GABA neurons.
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DOI：
10.1111/j.1530-0277.2009.00899.x
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Steffensen SC
中科院分区：
文献类型：
--
作者：
Ludlow KH;Bradley KD;Allison DW;Taylor SR;Yorgason JT;Hansen DM;Walton CH;Sudweeks SN;Steffensen SC
腹侧被盖区(VTA) γ-氨基丁酸（GABA）神经元似乎是乙醇对涉及药物奖励的中皮质边缘系统多巴胺（DA）神经传递的急性和慢性影响的关键底物。急性乙醇可降低VTA - GABA神经元的放电速率，而DA可通过D2受体激活增强其放电速率。本研究的目的是评估D2受体在急性乙醇抑制VTA - GABA神经元活性中的作用，以及D2受体在慢性乙醇消耗中的适应性。利用电生理方法，我们评估了腹腔内乙醇对VTA GABA神经元DA激活的影响，DA拮抗剂对乙醇抑制其放电速率的影响，以及慢性乙醇消耗后放电速率的适应性。使用单细胞定量rt -聚合酶链反应（PCR），我们评估了饮用乙醇的大鼠与成对喂养的对照组中VTA - GABA神经元D2受体的表达。在急性乙醇研究中，急性腹腔注射乙醇可抑制DA对VTA GABA神经元的微电泳激活，静脉注射D2拮抗剂依替氯pride可阻断乙醇对VTA GABA神经元放电速率的抑制。在慢性乙醇研究中，虽然在24小时内没有戒断的迹象，也没有明显的放电速率或对急性乙醇的反应的适应，但与成对喂养的对照组相比，摄入乙醇的大鼠D2受体的表达明显下调。乙醇抑制VTA GABA神经元放电速率的DA激活，以及依替氯pride阻断乙醇对VTA GABA神经元放电速率的抑制，表明乙醇与DA神经传递通过D2受体之间存在相互作用，可能是通过乙醇抑制GABA神经元后VTA中DA释放增强。慢性乙醇对VTA - GABA神经元D2受体的下调可能与持续向GABA神经元释放DA有关。
Ventral tegmental area (VTA) γ-aminobutyric acid (GABA) neurons appear to be critical substrates underlying the acute and chronic effects of ethanol on dopamine (DA) neurotransmission in the mesocorticolimbic system implicated in drug reward. VTA GABA neuron firing rate is reduced by acute ethanol and enhanced by DA via D2 receptor activation. The objective of this study was to evaluate the role of D2 receptors in acute ethanol inhibition of VTA GABA neuron activity, as well as the adaptation of D2 receptors by chronic ethanol consumption. Using electrophysiological methods, we evaluated the effects of intraperitoneal ethanol on DA activation of VTA GABA neurons, the effects of DA antagonists on ethanol inhibition of their firing rate, as well as adaptations in firing rate following chronic ethanol consumption. Using single cell quantitative RT-polymerase chain reaction (PCR), we evaluated the expression of VTA GABA neuron D2 receptors in rats consuming ethanol versus pair-fed controls. In acute ethanol studies, microelectrophoretic activation of VTA GABA neurons by DA was inhibited by acute intraperitoneal ethanol, and intravenous administration of the D2 antagonist eticlopride blocked ethanol suppression of VTA GABA neuron firing rate. In chronic ethanol studies, while there were no signs of withdrawal at 24 hours, or significant adaptation in firing rate or response to acute ethanol, there was a significant down-regulation in the expression of D2 receptors in ethanol-consuming rats versus pair-fed controls. Inhibition of DA activation of VTA GABA neuron firing rate by ethanol, as well as eticlopride block of ethanol inhibition of VTA GABA neuron firing rate, suggests an interaction between ethanol and DA neurotransmission via D2 receptors, perhaps via enhanced DA release in the VTA subsequent to ethanol inhibition of GABA neurons. Down-regulation of VTA GABA neuron D2 receptors by chronic ethanol might result from persistent DA release onto GABA neurons.
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DOI：
10.1097/00000374-199911000-00019
发表时间：
1999-11-01
影响因子：
3.2
作者：
Brodie, MS;Pesold, C;Appel, SB
通讯作者：
Appel, SB
影响因子：
5.5
作者：
JOHNSON, SW;NORTH, RA
通讯作者：
NORTH, RA
影响因子：
5
作者：
HYYTIA, P;KOOB, GF
通讯作者：
KOOB, GF
影响因子：
2.3
作者：
Eiler, WJA;Seyoum, R;June, HL
通讯作者：
June, HL
影响因子：
3.6
作者：
AGMO, A;GALVAN, A;TALAMANTES, B
通讯作者：
TALAMANTES, B