Fig. 2.

The hypothalamic pituitary adrenal (HPA) axis is functionally different depending on an individual’s prior experience with alcohol. Data were obtained from adult male rats that were either naïve (no operant training or previous exposure to alcohol), low-drinking non-dependent (several weeks of low levels of alcohol-self administration), non-dependent (several weeks of moderate levels of alcohol-self administration), or dependent (several weeks of moderate levels of alcohol self-administration followed by chronic alcohol vapor-induced dependence). All measures were taken when dependent animals were in acute withdrawal (6–8 hours after removal from chronic alcohol vapors). (A) The level of dampened HPA activity in response to 1 g/kg iv alcohol challenge depends on animals’ alcohol responsiveness and the alcohol exposure history. (B) CRF mRNA expression is low in the hypothalamus of dependent compared to alcohol-naïve controls, and CRF mRNA expression in non-dependent animals is intermediate to these two groups. (C) A CRF challenge (0.3 µg/kg, iv) elicits a lower ACTH response in drinking rats relative to alcohol-naïve controls, but the non-dependent and dependent groups do not differ from one another. Abbreviations: iv, intravenous; pPVN, parvocellular division of paraventricular nucleus of the hypothalamus; mPVN, magnocellular division of PVN; 3V, third ventricle. [Adapted from Richardson et al., 2008 European Journal of Neuroscience.]