Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration.

Increased ataxia and sedation after acute ethanol administration in GABAA α2-subunit KO mice.(A) Latency (secs) to fall from the Rotarod apparatus. WT mice are able to remain on the Rotarod apparatus for longer than KO after 2 g/kg ethanol (n = 10; genotype by time interaction, F(6,108) = 3.703, p<0.05, ε = 0.604) (B) Latency (secs) to fall from the wire hang apparatus. WT mice are able to retain a grip on the hanging wire longer than KO mice after 2 g/kg ethanol. (n = 12; genotype by time interaction, F(2,44) = 3.133, p = 0.05) (C) Loss of righting reflex. KO animals show a longer duration of sedation after 3.5 g/kg ethanol (n = 12; t(22) = −4.4, p<0.001) (D) Locomotor dose response. KO animals show reduced locomotion at 5 mins after 3 g/kg ethanol when compared to WT animals (n = 8; genotype by dose interaction, F(3,39) = 3.075, p<0.05).

Self administration of sucrose/ethanol solution remains unchanged in GABAA α2-subunit KO mice.(A) Sessions to criteria. The genotypes did not differ in their acquisition of self administration, performing a similar number of sessions to criteria at each concentration of ethanol (n = 8; 10%0%: U = 31.5, p = 0.648; 10%3%: U = 28.0, p = 1.00; 10%5%: U = 22.5, p = 0.448; 7%5%: U = 27.5, p = 0.951; 10%10%: U = 28.0, p = 1.00) (B) Number of active lever presses. Both genotypes perform a comparable number of lever presses to obtain increasing concentrations of ethanol in a sucrose/ethanol solution (genotype by reinforcer interaction, F(4,52) = 0.721, p = 0.486, ε = 0.462) (C) Number of reinforcers earned. Both WT and KO mice earned a similar number of reinforcers at each concentration of ethanol (genotype by reinforcer interaction, F(4,52) = 0.486, p = 0.604, ε = 0.456), indicating that motivation to obtain ethanol is unchanged after a deletion of the GABAA α2-subunit.

Blood ethanol concentration.Following an acute ethanol challenge (2 g/kg, i.p.), no genotype differences were observed in blood ethanol concentration (n = 4; genotype by sampling time interaction F(2,15) = 0.005, p = 0.995).