Oxytocin prevents ethanol actions at δ subunit-containing GABAA receptors and attenuates ethanol-induced motor impairment in rats
Abstract
Even moderate doses of alcohol can cause considerable motor impairment. This effect has been linked to ethanol-induced potentiation of GABA actions at δ subunit-containing GABAA receptors (δ-GABAARs). Here, we demonstrate that the neuropeptide oxytocin selectively attenuates ethanol-induced motor impairment in rats as well as ethanol-induced potentiation of GABAergic activity at δ-GABAARs. This effect of oxytocin is shown to be independent of the oxytocin receptor (OTR) and involves a direct action at δ-GABAARs. To our knowledge, this study provides the first evidence of oxytocin having a direct, non-OTR-mediated effect on GABA-ethanol interactions. Recent preclinical and clinical studies indicate that oxytocin may also attenuate alcohol consumption, craving, and withdrawal, and the present study shows a previously unidentified mechanism through which some of these effects may occur.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2015
- DOI:
- 10.1073/pnas.1416900112
- Bibcode:
- 2015PNAS..112.3104B