Cocaine-induced plasticity of intrinsic membrane properties in prefrontal cortex pyramidal neurons: Adaptations in potassium currents
Cocaine-induced plasticity of intrinsic membrane properties in prefrontal cortex pyramidal neurons: Adaptations in potassium currents
复制标题
DOI：
10.1523/jneurosci.4715-04.2005
复制
发表时间：
2005-01-26
影响因子：
5.3
通讯作者：
White, FJ
中科院分区：
文献类型：
--
作者：
Dong, Y;Nasif, FJ;White, FJ
前额叶皮质（PFC）中药物诱导的适应有助于成瘾行为的几个核心方面，但潜在的神经元过程基本上仍然未知。在这里，我们证明了体内反复暴露于可卡因持续降低PFC锥体神经元的电压门控K（+）电流（VGKC），导致膜兴奋性增强。对多巴胺D-1类受体（D1R）介导的VGKC调节的分析表明，尽管没有直接的D1R刺激，但在慢性可卡因治疗戒断期间，下游D-1信号（cAMP/蛋白激酶A途径）增加，并在药物诱导的pfc膜可塑性中起核心作用。可卡因诱导的PFC锥体神经元膜兴奋性的可塑性可能有助于可卡因戒断的决策和药物渴望受损。
Drug- induced adaptations in the prefrontal cortex ( PFC) contribute to several core aspects of addictive behaviors, but the underlying neuronal processes remain essentially unknown. Here, we demonstrate that repeated in vivo exposure to cocaine persistently reduces the voltage- gated K (+) current ( VGKC) in PFC pyramidal neurons, resulting in enhanced membrane excitability. Analysis of dopamine D-1- class receptor ( D1R)- mediated modulation of VGKC indicates that, despite the absence of direct D1R stimulation, downstream D-1 signaling ( the cAMP/ protein kinase A pathway) is increased during withdrawal from chronic cocaine treatment and plays a central role in the drug- induced membrane plasticity in PFC. This long- lasting, cocaine- induced plasticity of membrane excitability in PFC pyramidal neurons may contribute to the impaired decision making and drug craving that characterize cocaine withdrawal.