Additional labeling studies with phenotypic makers for immature neurons, mature neurons, astrocytes and oligodendrocytes in the mPFC will also allow us to delineate specific effects of alcohol dependence on the phenotype of surviving cortical precursors. Nondependent drinking showed a trend towards decrease in proliferation with no effect on survival. It is possible that larger sample sizes would allow for the detection of reduced Ki-67 cells in the mPFC of nondependent animals to suggest that moderate alcohol exposure also impacts proliferation. Both nondependent drinking and alcohol dependence reduced apoptosis, perhaps indicating compensation of the mPFC gliogenic niche and predicting the eventual neurotoxic response to chronic alcohol after extended intake. This hypothesis is supported by the opposing effects of prolonged alcohol dependence on proliferation. For example, early dependence (6 weeks of vapors) reduced proliferation and the reduction was normalized after 4 weeks of further exposure to alcohol vapors. The normalization of proliferation after prolonged dependence suggests that compensatory mechanisms (e.g., further decreases in cell death) may be enhanced during the additional 4 weeks of exposure to intermittent alcohol vapors to reverse the negative effects of alcohol on proliferation. An alternative explanation is that the effects of alcohol on proliferation during dependence may
