Animal models of nondependent drinking and excessive drinking during alcohol dependence are useful in modeling distinct patterns of alcohol use in humans that range from casual drinking to alcoholism. The present study shows that chronic drinking alters adult neurogenesis in the hippocampus prior to dependence– suggesting that alcohol-induced changes in neurogenesis may proceed and possibly cause the neurodegeneration and hippocampal deficits associated with chronic alcoholism. Notably, alcohol dependence reduces proliferative capacity in the prefrontal cortex and hippocampus with distinct underlying mechanisms specific to each brain region. For example, nondependent drinking and alcohol dependence reduced cortical apoptosis, which might serve to compensate for the toxic effects of alcohol on existing neurons, as suggested in a recent report showing down-regulation of apoptotic pathways in alcoholics (Johansson et al., 2009). Alcohol dependence produced no change in hippocampal apoptosis but increased neuronal degeneration, indicating that the later stages of chronic high alcohol use and dependence are characterized by increased cell death via non-apoptotic pathways, decreasing neuronal turnover in the hippocampus. Such regulation by alcohol dependence in the two brain regions suggests that proliferating cells from each region may play critical roles in the consequences of long-term exposure to alcohol associated with dependence.
