Editors' ChoiceNeuroscience

GABA receptors as oxytocin targets

Science Signaling  17 Mar 2015:
Vol. 8, Issue 368, pp. ec60
DOI: 10.1126/scisignal.aab1171

Prominent effects of alcohol intoxication are increased sociability, loss of motor coordination, and sleepiness. Bowen et al. found that injecting oxytocin, a neuromodulatory hormone that promotes social behaviors, in the brains of rats prior to administration of ethanol reduced the sedating and motor impairment effects. The GABAA receptor is a ligand-gated Cl channel that suppresses neuronal activity and is also a site of ethanol’s actions in the brain. Analysis of various combinations of subunits of the GABAA receptor expressed in Xenopus oocytes showed that the ethanol-potentiating effects and oxytocin’s ability to reduce these effects required the δ subunit. Oxytocin did not affect GABAA currents in the absence of both GABA and ethanol. The inhibitory effect of oxytocin on the δ subunit-containing receptors appeared specific for ethanol, because the potentiating effects of a GABAA agonist that binds a different site from ethanol on the δ receptor were unaffected by oxytocin either in animal behavior tests or in the Xenopus expression system. Because Xenopus oocytes do not have the oxytocin receptor, these data indicate that oxytocin exerted its effects independently from the oxytocin receptor and suggest that the δ subunit of GABAA may be a target of oxytocin action.

M. T. Bowen, S. T. Peters, N. Absalom, M. Chebib, I. D. Neumann, I. S. McGregor, Oxytocin prevents ethanol actions at δ subunit-containing GABAA receptors and attenuates ethanol-induced motor impairment in rats. Proc. Natl. Acad. Sci. U.S.A. 112, 3104–3109 (2015). [Abstract] [Full Text]