GABA transporter currents activated by protein kinase A excite
midbrain neurons during opioid withdrawal
by
Bagley EE, Gerke MB, Vaughan CW, Hack SP, Christie MJ.
Pain Management Research Institute at Royal North Shore Hospital,
The University of Sydney,
NSW 2006, Australia.
bagleye@med.usyd.edu.au
Neuron. 2005 Feb 3;45(3):433-45.

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.

Lofexidine
Oxycodone
Endomorphins
Novelty and pain
Fentanyl and ketamine
Signalling mechanisms
The extended amygdala
Opioids, mood and cognition
Tolerance, sensitization and dependence
Nucleus accumbens shell/medium spiny neurons
Alpha-2 adrenergic agonists for opioid withdrawal
Use of non-opioid drugs for opioid withdrawal symptoms

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