K_Ca2 channels: Novel therapeutic targets for treating alcohol withdrawal and escalation of alcohol consumption

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• 作者：Patrick J. Mulholland ; ^{mulholl@musc.edu}
• 关键词：SK channels ; Ethanol withdrawal ; Ca2+-activated K+ channels ; Alcohol dependence ; Adaptive plasticity ; Withdrawal hyperexcitability ; Alcohol consumption
• 刊名：Alcohol
• 出版年：2012
• 期刊代码：1_07418329
• 类别：neu
• 出版时间：June, 2012
• 卷：46
• 期：4
• 页码：309-315
• 文件大小：298 K

摘要

Small-conductance, calcium-activated potassium (K_Ca2) channels influence neuronal firing properties, intrinsic excitability, and NMDA receptor-dependent synaptic responses and plasticity. In this mini-review, we discuss new evidence that chronic alcohol-associated plasticity critically involves K_Ca2 channels in hippocampus, ventral tegmental area, and nucleus accumbens. K_Ca2 channel activity can modulate the magnitude of excitation of midbrain dopamine neurons induced by acute alcohol exposure. Emerging evidence indicates that K_Ca2 channels regulate neuroadaptations to chronic alcohol that contribute to withdrawal hyperexcitability and escalation of voluntary alcohol consumption. Restoring K_Ca2 channel activity can attenuate the severity of the alcohol withdrawal syndrome in vivo and withdrawal-associated neurotoxicity in vitro. Pharmacological modulation of K_Ca2 channels can bi-directionally influence drinking behavior in rat and mouse models of voluntary alcohol consumption. Collectively, these studies using various rodent models have clearly indicated a central role for K_Ca2 channels in the neuroplasticity of chronic alcohol exposure. In addition, accumulating evidence suggests that K_Ca2 channels are a novel therapeutic target to alleviate the symptoms of alcohol withdrawal and reduce high amounts of alcohol drinking.