| First Author | Darnieder LM | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 8102 |
| PubMed ID | 31147611 | Mgi Jnum | J:281480 |
| Mgi Id | MGI:6357333 | Doi | 10.1038/s41598-019-44286-0 |
| Citation | Darnieder LM, et al. (2019) Female-specific decreases in alcohol binge-like drinking resulting from GABAA receptor delta-subunit knockdown in the VTA. Sci Rep 9(1):8102 |
| abstractText | Binge drinking is short-term drinking that achieves blood alcohol levels of 0.08 g/dl or above. It exhibits well-established sex differences in GABAergic inhibitory neurotransmission, including extrasynaptic delta subunit-containing GABAA receptors (delta-GABAARs) that mediate tonic inhibition, or synaptic gamma2-containing GABAARs which underlie fast, synaptic, phasic inhibition have been implicated in sex differences in binge drinking. Ovarian hormones regulate delta-GABAARs, further implicating these receptors in potential sex differences. Here, we explored the contribution of extrasynaptic delta-GABAARs to male and female binge-like drinking in a critical area of mesolimbic circuitry-the ventral tegmental area (VTA). Quantitative PCR revealed higher Gabrd transcript levels and larger tonic currents in the VTA of females compared to males. In contrast, male and female Gabrg2 transcript levels and measures of phasic inhibition were equivalent. Intra-VTA infusion of AAV-Cre-GFP in floxed Gabrd mice downregulated delta-GABAARs and decreased binge-like drinking in females. There was no significant difference in either male or female mice after GABAAR gamma2 subunit reduction in the VTA following AAV-Cre-GFP infusion in floxed Gabrg2 mice. Collectively, these findings suggest sex differences and GABAAR subunit specificity in alcohol intake. |
