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We have examined if age-related deterioration of spatial memory and cholinergic innervation of the dentate gyrus is gender-specific. Aging progressively affected the performance of male and female rats in place discrimination version of the water maze task. On repeated acquisition task, only old males, but not old females, were significantly impaired relative to young and adult animals of both sexes. In parallel, we found that the age-associated reduction of the density of cholinergic fibers in the dentate gyrus was significantly more profound in old males than in age-matched females. These results suggest that, although male and female rats have an identical pattern of reference memory decline, impairment of the working memory and deterioration of the hippocampal cholinergic system are slower to develop in females than in males.

Using the unbiased disector method we have shown that chronic alcohol consumption induces a significant decrease of dentate gyrus granule cell density in alcohol-fed rats for 18 months. A still more dramatic reduction was observed in a group of age-matched rats alcohol-fed for 12 months and switched to water for 6 months (recovery group). These results indicate that a progressive neuronal loss of the hippocampal granule cells in not impeded after cessation of alcohol intake. It is thus suggested that once the mechanisms underlying the alcohol-induced neuronal degeneration are triggered, they continue to act even after withdrawal.

Alcohol consumption in rats leads to degenerative changes in the cerebellar cortex (described elsewhere). Purkinje cells show a loss of dendritic spines, but some of the intact spines elongate to 3-4 times their normal length. This is postulated as a plastic change resulting from the degeneration of the original axon terminal contact with a consequent elongation of the spine 'in search of' and finally synapsing with still viable parallel fibre terminals in the vicinity. Under these conditions the circuitry is radically altered.

Multivesicular bodies (MVBs) with diameters up to 4.5 microns were observed in the hippocampal pyramidal cells of rats submitted to chronic alcohol consumption. A significant increase in the volumetric density (Vv) of these organelles was found in CA1 pyramidal cells. Transitional forms of MVBs towards lysosomes were seen. A failure in MVB's enzymatic hydrolytic mechanisms, due to the prolonged alcohol aggression, could underlie its formation.