@article {Blednovjpet.111.185124, author = {Yuri A. Blednov and Jill M. Benavidez and Gregg E. Homanics and R. Adron Harris}, title = {Behavioral characterization of knockin mice with mutations M287L and Q266I in the glycine receptor α1 subunit}, elocation-id = {jpet.111.185124}, year = {2011}, doi = {10.1124/jpet.111.185124}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {We used behavioral pharmacology to characterize heterozygous knockin mice with mutations (Q266I or M287L) in the α1 subunit of the glycine receptor (GlyR) (Borghese et al., companion paper). These mutations were designed to reduce (M287L) or eliminate (Q266I) ethanol potentiation of glycine receptor function. We asked which behavioral effects of ethanol would be reduced more in the Q266I mutant than the M287L, and found rotarod ataxia to be the behavior that fulfilled this criterion. Compared to controls, the mutant mice also differed in ethanol consumption, ethanol-stimulated startle response, signs of acute physical dependence and duration of loss of righting response produced by ethanol, butanol, ketamine, pentobarbital and flurazepam. Some of these behavioral changes were mimicked in wild-type mice by acute injections of low, subconvulsive doses of strychnine. Both mutants showed increased acoustic startle response and increased sensitivity to strychnine seizures. Thus, in addition to reducing ethanol action on the GlyRs, these mutations reduced glycinergic inhibition which may also alter sensitivity to GABAergic drugs.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/early/2011/10/28/jpet.111.185124}, eprint = {https://jpet.aspetjournals.org/content/early/2011/10/28/jpet.111.185124.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }