Reduced hippocampal neurogenesis with alcohol self-administration and dependence may promote hippocampal neuronal loss through multiple mechanisms. Studies using forced alcohol paradigms to investigate the effect of alcohol on neural plasticity have suggested that alcohol reduces proliferation and neurogenesis in the adult hippocampus through increased cell death (He et al., 2005; Herrera et al., 2003; Obernier et al., 2002). Active programmed cell death (apoptosis) and neuronal degeneration were analyzed in the present study. Nondependent drinking increased hippocampal apoptosis. Apoptotic cell death was not observed in dependent animals but increased neuronal degeneration was evident, suggesting that cells may be dying in dependent animals through other cell death pathways. Long-term exposure to moderate to high alcohol may produce cell death via apoptosis and necrosis (Obernier et al., 2002), which could underlie decreased granule cell number and eventual decreases in hippocampal volume. Perhaps, nondependent drinking first initiates programmed cell death, which is then followed by passive non-programmed degeneration of neurons with increasing alcohol exposure during dependence.
