EFFECTS OF CHRONIC ETHANOL INGESTION ON LONG-TERM POTENTIATION REMAIN EVEN AFTER A PROLONGED RECOVERY FROM ETHANOL EXPOSURE

Previous work in our laboratory has demonstrated that memory formation, a behavioral process thought to be at least in part attributed to hippocampal functioning, is severely attenuated following 5 months of chronic ethanol treatment (CET) and 2 months of recovery from CET. Additionally, 48 h following CET, a well-recognized physiological correlate of memory formation, long-term potentiation (LTP), is reduced in the hippocampus. We hypothesized that the reduction in LTP may in part contribute to the behavioral deficit in memory formation, which is a permanent consequence of CET. In order for the reduction of LTP to be involved with the permanent deficit in memory acquisition, it too must be present following a prolonged period of ethanol abstinence. The present study examined the permanent effect of CET on LTP. Animals were fed a nutritionally complete, ethanol containing diet for 28 weeks and then allowed a 5-7 month abstinence period. A control group was fed the same diet except sucrose was isocalorically substituted for ethanol. Neurophysiological methods measured the capacity of synaptic connections onto CA1 pyramidal cells to support LTP in response to a variety of conditioning trains. The magnitude of LTP was reduced in CET animals as compared with pair-fed controls. LTP induction is mediated by activation of the N-methyl-d-aspartate (NMDA) receptor complex and is modulated by activation of gamma-aminobutyric acid (GABA)ergic synaptic transmission. The effect of CET on LTP magnitude may be due to effects on the NMDA-induced induction itself or on the GABAergic modulation of induction. To distinguish between these possibilities, the induction of LTP was tested in the presence of bicuculline methiodide (a specific antagonist to the GABA, receptor). Under these conditions, the ethanol-induced deficit in LTP was abolished. On the basis of these results we hypothesized that the CET reduction in LTP magnitude observed in the absence of bicuculline was due to a permanent alteration of GABAergic modulation of LTP induction. Portions of this paper have been presented previously in abstract form [Tremwel and Hunter (1990), Sec. Neurosci Abstr., 980]. (C) 1994 Wiley-Liss, Inc.