Abstract：
:Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly increased GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG) during opioid withdrawal in rodents. In contrast, GAT-1 did not indirectly alter GABA receptor responses via modulation of extracellular GABA concentrations. Notably, we found that GAT-1-induced increases in GABAergic activity contributed to many PAG-mediated signs of opioid withdrawal. Together, these data support the hypothesis that GAT-1 activity directly produces opioid withdrawal signs through direct hyperexcitation of GABAergic PAG neurons and nerve terminals, which presumably enhances GABAergic inhibition of PAG output neurons. These data provide, to the best of our knowledge, the first evidence that dysregulation of a neurotransmitter transporter current is important for the maladaptive plasticity that underlies opiate withdrawal.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Bagley EE,Hacker J,Chefer VI,Mallet C,McNally GP,Chieng BC,Perroud J,Shippenberg TS,Christie MJdoi
10.1038/nn.2940subject
Has Abstractpub_date
2011-10-30 00:00:00pages
1548-54issue
12eissn
1097-6256issn
1546-1726pii
nn.2940journal_volume
14pub_type
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