Behavioural changes produced by transgenic overexpression of gamma 2L and gamma 2S subunits of the GABA(A) receptor

Transgenic mice overexpressing either the mouse gamma 2L or gamma 2S subuni t of the GABA(A) receptor were generated in a C57BL/6 J x DBA/2 J mixed bac kground and expanded into transgenic lines. Transgenic mice and littermate controls were analysed with respect to altered behaviour indicative of anxi ety, motor activity and acute effects of benzodiazepines and alcohol, as we ll as with regard to altered responses to alcohol withdrawal and acute func tional tolerance to alcohol. Biochemical tests assessed flunitrazepam- and ethanol-enhanced Cl-36(-) flux stimulated by muscimol in cerebellar and cor tical microsacs and [H-3]-flunitrazepam binding to cerebellar membranes. Th ere were no significant differences in any of these measures between the tr ansgenic and control mice, except in tests of acute functional tolerance to acute injection of ethanol. Compared to controls, mice carrying either the gamma 2L or gamma 2S transgene developed significantly less tolerance to t he ataxic effects of ethanol. We conclude that acute functional tolerance t o ethanol is very sensitive to the amount of GABA(A) receptor gamma 2 subun it available (regardless of whether it is gamma 2L or gamma 2S) but overexp ression of neither subunit isoform alters other behavioural and biochemical phenotypes.