GABA transporter currents activated by protein kinase a excite midbrain neurons during opioid withdrawal
GABA transporter currents activated by protein kinase a excite midbrain neurons during opioid withdrawal
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DOI：
10.1016/j.neuron.2004.12.049
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发表时间：
2005-02-03
期刊：
影响因子：
16.2
通讯作者：
Christie, MJ
中科院分区：
文献类型：
--
作者：
Bagley, EE;Gerke, MB;Christie, MJ
Adaptations in neurons of the midbrain periaqueductal gray (PAG) induced by chronic morphine treatment mediate expression of many signs of opioid withdrawal. The abnormally elevated action potential rate of opioid-sensitive PAG neurons is a likely cellular mechanism for withdrawal expression. We report here that opioid withdrawal in vitro induced an opioid-sensitive cation current that was mediated by the GABA transporter-1 (GAT-1) and required activation of protein kinase A (PKA) for its expression. Inhibition of GAT-1 or PKA also prevented withdrawal-induced hyperexcitation of PAG neurons. Our findings indicate that GAT-1 currents can directly increase the action potential rates of neurons and that GAT-1 may be a target for therapy to alleviate opioid-withdrawal symptoms.
