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 stimulati
on of the perforant path. Dentate evoked responses were recorded durin
g a 3 h session in which rats pressed a lever on a fixed interval (30
s) schedule of reinforcement. Following theta-pattern stimulation, rat
s pretreated with saline had significant LTP that was present througho
ut the session. LTP was measured as an increase in the initial slope a
nd the population spike of the evoked response. The potentiation was n
o longer present 24 h after stimulation. Ethanol (0.5 g/kg and 1.0 g/k
g) blocked LTP and attenuated short-term frequency potentiation in a d
ose-dependent fashion. Although ethanol produced a decrease in rewarde
d lever pressing, lever pressing was not correlated to any measure of
the evoked response. Ethanol, when given 60 min after theta-pattern st
imulation, did not alter the expression of LTP. The results demonstrat
e that low doses of ethanol selectively blocked the induction of LTP i
n vivo, an effect that may underlie ethanol's impairment of memory.