As previously noted, alcohol activates the HPA axis, with the magnitude and response profile influenced by a host of variables (Lu and Richardson, 2014; Rivier, 2000; Wand, 2000). These include a number of alcohol-related factors (e.g., history of use, level and pattern of drinking, timing of accessibility of alcohol in relation to stress experience) as well as stress-related factors (e.g., type, chronicity, intermittency, predictability, controllability) that intersect with a number of biological variables (e.g., genetics, age, sex). As reported in clinical studies, experimental studies have documented profound disturbances in HPA axis function following chronic alcohol exposure and withdrawal. For example, studies in rodents have shown that chronic alcohol consumption results in a general elevation in blood corticosteroid levels, with a typical flattening of normal circadian fluctuations (Kakihana and Moore, 1976; Keith and Crabbe, 1992; Rasmussen et al., 2000; Tabakoff et al., 1978). At the same time, there is a dampened HPA response to subsequent CRF or stress challenge (Lee et al., 2000; Rivier et al., 1990). Additionally, the ability of alcohol to activate the HPA axis is blunted following chronic
