Fyn knockout mice and mice that overexpress Fyn under control of an αCaMKII promoter in the forebrain, amygdala, and hippocampus (OVF mice) have been used to investigate the role of Fyn in behavioral responses to ethanol. Homozygous Fyn knockout mice show an increase,272,273 and OVF mice show a decrease, in the duration of the ethanol-induced LORR274 when compared with their corresponding wild-type littermates. Homozygous Fyn knockout mice also show an increase in the duration of ethanol-induced LORR when compared with heterozygous Fyn knockout mice269 or wild-type littermates.272 Neither Fyn knockout mice272,273 nor OVF mice274 show differences in ethanol clearance or initial sensitivity to ethanol. Fyn modulation of NMDA receptor activity may contribute to differences in acute sensitivity to the hypnotic effects of ethanol, since pretreatment with the NR2B-containing NMDA receptor antagonist ifendopril increases the duration of ethanol-induced LORR in wild-type mice to levels seen in homozygous Fyn knockout mice.272 Fyn knockout mice show decreased acute functional tolerance to ethanol, which contributes to their enhanced response to hypnotic doses of ethanol.273 They also show a greater anxiolytic effect of ethanol compared with wild-type mice on the elevated plus-maze, possibly due to an increased basal level of anxiety-like behavior.273
