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Updated: Aug 19, 2026

Whole-cell Currents Induced by Puff Application of GABA in Brain Slices
Published on: October 12, 2017
GABA transporter currents activated by protein kinase A excite midbrain neurons during opioid withdrawal
Elena E Bagley1, Michelle B Gerke, Christopher W Vaughan
1Pain 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.
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