Ethanol excitation of dopaminergic ventral tegmental area neurons is blocked by quinidine
Ethanol excitation of dopaminergic ventral tegmental area neurons is blocked by quinidine
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DOI：
10.1124/jpet.103.050963
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发表时间：
2003-08-01
影响因子：
3.5
通讯作者：
Brodie, MS
中科院分区：
文献类型：
--
作者：
Appel, SB;Liu, ZP;Brodie, MS
腹侧被盖区（VTA）的多巴胺能（DA）神经元在乙醇的强化作用中起重要作用。我们已经证明，乙醇直接刺激DA - VTA神经元，并减少这些神经元自发动作电位后的超极化（AHP）。这些数据表明，乙醇可能通过降低K+电流或增加1h内向电流来调节有助于AHP的电流，从而增加DA VTA神经元的放电速率。在本研究中，我们测试了不同的K+通道和1h阻滞剂，以确定是否有任何一种可以阻止乙醇对DA VTA神经元的激发。对fisher -344大鼠脑切片的DA - VTA神经元进行细胞外单单元记录和全细胞膜片钳记录，泡液中应用乙醇（40-120 mM）和通道阻滞剂。用铯（5 mM）或ZD7288 （30 muM）阻断1 h，或用钡（500 muM）阻断g蛋白偶联的向内整流K+通道，均不降低乙醇激发。四乙基铵（TEA）离子（2-10 mM）阻断了大电导钙依赖性钾离子K+电流和某些类型的延迟整流电流，对乙醇激发没有影响。有趣的是，DA - VTA神经元的乙醇兴奋被奎尼丁（20-80 muM）阻断，奎尼丁是一种阻断多种延迟整流K+通道的药物，包括一些对TEA不敏感的通道。奎尼丁的这种作用具有浓度依赖性和可逆性。这些结果表明，乙醇通过降低奎尼丁敏感的K+电流来刺激DA - VTA神经元。
The dopaminergic (DA) neurons in the ventral tegmental area (VTA) are important for the reinforcing effects of ethanol. We have shown that ethanol directly excites DA VTA neurons and reduces the afterhyperpolarization (AHP) that follows spontaneous action potentials in these neurons. These data suggested that ethanol may be increasing the firing rate of DA VTA neurons by modulating currents that contribute to the AHP, either by reducing a K+ current or by increasing the inward current 1 h. In the present study, different blockers of K+ channels and 1 h were tested to determine whether any could prevent the ethanol excitation of DA VTA neurons. Extracellular single-unit recordings and whole-cell patch-clamp recordings were made from DA VTA neurons in brain slices from Fischer-344 rats and ethanol (40-120 mM) and channel blockers were applied in the bath. Ethanol excitation was not reduced by blockade of 1 h with cesium (5 mM) or ZD7288 (30 muM), or by block of G-protein-coupled inwardly rectifying K+ channels with barium (500 muM). Tetraethylammonium (TEA) ion (2-10 mM), which blocks the large conductance calcium-dependent potassium K+ current and some types of delayed rectifier currents, had no effect on the ethanol-induced excitation. Interestingly, ethanol excitation of DA VTA neurons was blocked by quinidine (20-80 muM), a drug that blocks many types of delayed rectifier K+ channels, including some insensitive to TEA. This effect of quinidine was concentration-dependent and reversible. These results suggest that ethanol excites DA VTA neurons by reducing a quinidine-sensitive K+ current.