Chronic ethanol consumption in rats results in blunted elevation of cerebral cortical 3α,5α-THP (Morrow et al. 2001) and plasma and brain deoxycorticosterone levels following acute ethanol challenge (Khisti et al. 2005) compared to pair-fed control rats. These findings suggest that there is tolerance to ethanol-induced increases in neuroactive steroid levels. The loss of ethanol-induced increases in neuroactive steroids may contribute to ethanol tolerance since the elevations of neuroactive steroids are required for anxiolytic, sedative, anticonvulsant, and cognitive-impairing effects of ethanol. Furthermore, since decreases in brain neuroactive steroid levels are concomitant with decreases in plasma neuroactive steroid levels, it is likely that the observed decreases in 3α,5α-THP and deoxycorticosterone levels are dependent on blunted HPA axis activity. It is well known that chronic stress results in adaptation of the HPA axis leading to decreases in stress-induced changes in the levels of corticosterone in rats (Spencer and McEwen 1990). This blunting of the HPA axis is associated with a reduction in corticotrophin releasing factor and adrenocorticotropin releasing hormone elevations following ethanol challenge (Lee et al. 2001). Furthermore, repeated ethanol withdrawal also leads
