K Ca2 channels: Novel therapeutic targets for treating alcohol withdrawal and escalation of alcohol consumption

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.