Investigation of ethanol-induced impairment of spatial memory in gamma2 heterozygous knockout mice

Abstract

GABA(A) receptors, the major inhibitory receptors in the mammalian central nervous system, are affected by a number of drug compounds, including ethanol. The pharmacological effects of certain drugs have been shown to be dependent upon specific GABA(A) receptor subunits. Because benzodiazepines and ethanol have similar effect signatures, it has been hypothesized that these drugs share the gamma2-containing GABA(A) receptors as a mechanism of action. To probe the involvement of the gamma2 subunit in ethanol's actions, spatial memory for the Morris water maze task was tested in gamma2 heterozygous knockout mice and wild type littermate controls following ethanol administration at the following doses: 0.0, 1.25, 1.75, and 2.25 g/kg. While baseline learning and memory were unaffected by reduction of gamma2 containing GABA(A) receptors, ethanol dose-dependently impaired spatial memory equally in gamma2 heterozygous knockouts and wild type littermate controls.

Figure 1

Blood Alcohol Content. Mean blood alcohol content values were measured in γ2 heterozygous knockout mice and wild type controls following acute ethanol administration for each dose. * 2.25 g/kg ethanol resulted in higher mean blood alcohol content than 1.75 g/kg and 1.25 g/kg ethanol (both p’s < 0.05). ** 1.75g/kg ethanol resulted in higher mean blood alcohol content than 1.25 g/kg ethanol (p < 0.05). Error bars represent S.E.M.

Figure 2

Spatial Learning. Mean path length values were measured for γ2 heterozygous knockout mice and wild type controls across training days in the Morris water maze spatial task. Mean path lengths decreased across training days (p < 0.05) but were not affected by genotype. Error bars represent S.E.M.

Figure 3

Ethanol Test Day. Mean path length values were measured for γ2 heterozygous knockout mice and wild type control mice in the ethanol challenge. * 2.25 g/kg ethanol resulted in higher mean path length scores compared to all other doses (all p’s < 0.05) Error bars represent S.E.M.