| First Author | Blednov YA | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 1 | Pages | e85525 |
| PubMed ID | 24454882 | Mgi Jnum | J:212189 |
| Mgi Id | MGI:5578275 | Doi | 10.1371/journal.pone.0085525 |
| Citation | Blednov YA, et al. (2014) GABAA receptors containing rho1 subunits contribute to in vivo effects of ethanol in mice. PLoS One 9(1):e85525 |
| abstractText | GABAA receptors consisting of rho1, rho2, or rho3 subunits in homo- or hetero-pentamers have been studied mainly in retina but are detected in many brain regions. Receptors formed from rho1 are inhibited by low ethanol concentrations, and family-based association analyses have linked rho subunit genes with alcohol dependence. We determined if genetic deletion of rho1 in mice altered in vivo ethanol effects. Null mutant male mice showed reduced ethanol consumption and preference in a two-bottle choice test with no differences in preference for saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration of ethanol-induced loss of righting reflex (LORR), and males were more sensitive to ethanol-induced motor sedation. In contrast, rho1 null mice showed faster recovery from acute motor incoordination produced by ethanol. Null mutant females were less sensitive to ethanol-induced development of conditioned taste aversion. Measurement of mRNA levels in cerebellum showed that deletion of rho1 did not change expression of rho2, alpha2, or alpha6 GABAA receptor subunits. (S)-4-amino-cyclopent-1-enyl butylphosphinic acid ("rho1" antagonist), when administered to wild type mice, mimicked the changes that ethanol induced in rho1 null mice (LORR and rotarod tests), but the rho1 antagonist did not produce these effects in rho1 null mice. In contrast, (R)-4-amino-cyclopent-1-enyl butylphosphinic acid ("rho2" antagonist) did not change ethanol actions in wild type but produced effects in mice lacking rho1 that were opposite of the effects of deleting (or inhibiting) rho1. These results suggest that rho1 has a predominant role in two in vivo effects of ethanol, and a role for rho2 may be revealed when rho1 is deleted. We also found that ethanol produces similar inhibition of function of recombinant rho1 and rho2 receptors. These data indicate that ethanol action on GABAA receptors containing rho1/rho2 subunits may be important for specific effects of ethanol in vivo. |
