GABA transporter currents activated by protein kinase A excite midbrain neurons during opioid withdrawal |
| |
Authors: | Bagley Elena E Gerke Michelle B Vaughan Christopher W Hack Stephen P Christie MacDonald J |
| |
Affiliation: | Pain Management Research Institute at Royal North Shore Hospital, The University of Sydney, NSW 2006, Australia. bagleye@med.usyd.edu.au |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |