Ethanol suppresses the induction of long-term potentiation in vivo.

Long-term potentiation (LTP), a leading neural mechanism of memory, is profoundly affected by ethanol in vitro, but ethanol's effect on LTP in vivo has not been studied at doses known to impair memory. In this study, LTP was induced in the dentate hilus by theta-pattern stimulation of the perforant path. Dentate evoked responses were recorded during a 3 h session in which rats pressed a lever on a fixed interval (30 s) schedule of reinforcement. Following theta-pattern stimulation, rats pretreated with saline had significant LTP that was present throughout the session. LTP was measured as an increase in the initial slope and the population spike of the evoked response. The potentiation was no longer present 24 h after stimulation. Ethanol (0.5 g/kg and 1.0 g/kg) blocked LTP and attenuated short-term frequency potentiation in a dose-dependent fashion. Although ethanol produced a decrease in rewarded lever pressing, lever pressing was not correlated to any measure of the evoked response. Ethanol, when given 60 min after theta-pattern stimulation, did not alter the expression of LTP. The results demonstrate that low doses of ethanol selectively blocked the induction of LTP in vivo, an effect that may underlie ethanol's impairment of memory.