Phase-specific impairment of fear memory and hippocampal synaptic potentiation in rats after prolonged ethanol exposure.

Abstract

Chronic alcohol consumption is known to impair cognitive function, but its effects on specific phases of memory processing remain incompletely understood. In the present study, we examined whether prolonged ethanol exposure alters associative fear memory and hippocampal synaptic plasticity. Rats were exposed to ethanol chronically and assessed using a fear conditioning paradigm. Chronic ethanol exposure selectively reduced the long-term expression of conditioned fear, while leaving acquisition and extinction learning largely intact. Electrophysiological recordings from hippocampal slices showed the significant attenuation of early-phase synaptic potentiation at Schaffer collateral-CA1 synapses in ethanol-exposed animals, whereas activity-dependent depotentiation was preserved. These findings indicate the selective impairment of the initial strengthening of synaptic responses accompanied by intact mechanisms for synaptic weakening. The dissociation between reduced potentiation and preserved depotentiation suggests that chronic ethanol exposure disrupts processes involved in the stabilization of newly formed memory traces, while sparing the mechanisms supporting the modification of existing memories. Together, our findings suggest that prolonged ethanol exposure preferentially compromises the mechanisms supporting the persistence of fear-based associative memory, while sparing memory acquisition, extinction, and activity-dependent synaptic weakening.