Joanna Peris, Kevin J. Anderson, Thomas W. Vickroy , Michael. A. King, Bruce E. Hunter and Don W. Walker

2. CET-INDUCED CHANGES IN MEMORY AND HIPPOCAMPAL FUNCTION

Long-term, excessive exposure to ethanol disrupts cognitive function as measured by a broad spectrum of techniques (1-4). The behavioral dysfunction can range from relatively mild cognitive deficits (4, 5) to Korsakoff’s syndrome or alcoholic dementia characterized by a profound anterograde amnesia (1, 4). The relative contribution of nutritional deficiency and ethanol neurotoxicity to the mnemonic deficit has not been established (2, 6). Further, a relationship between neuropathological alterations and specific memory dysfunction has not been adequately substantiated.

Numerous animal studies have confirmed that CET produces abnormal morphology and function in the rodent hippocampus (7). CET produces a progressive learning and memory deficit across a variety of behavioral tests including active avoidance (8-11), complex maze learning (12, 13), and tests of temporal (14, 15) and spatial (15-19) memory. The memory deficits grow progressively more severe with increasing exposure to CET and persist for prolonged periods following abstinence (8). Morphological changes in hippocampus associated with CET include a 10-40% loss of principal cells (16, 20-26) and interneurons (27, 28). The extent of the cell loss depends upon the duration of CET, the magnitude of exposure, genetic susceptibility to ethanol and the length of ethanol abstinence. For the purposes of this review, CET will be defined as continuous ethanol exposure for a sufficiently long period (e.g., 6 months) to result in lasting (or in some cases, permanent) structural and functional alterations of the hippocampus or its neural connections (7). At least 48 hrs withdrawal from ethanol is required so that the lasting functional disturbances associated with structural changes can be separated from the transient disturbances associated with ethanol tolerance and withdrawal (7). Periods of ethanol exposure that are not sufficient to cause persistent behavioral changes after withdrawal will be referred to as subchronic.

Neurons which survive CET also exhibit structural abnormalities (7). However, despite profound and often region-specific morphological changes (29-32), CET produces surprisingly subtle changes in the function of the hippocampus as directly assayed by electrophysiological methods. These functional changes include a reduction in intrinsic inhibitory processes (33-35) and a modification in the distribution of synaptic connections using current-source density analysis (36, 37).