At the same time, it is firmly established that alcohol, itself, is a stressor. Acute alcohol exposure activates the hypothalamic-pituitary-adrenocortical (HPA) axis, a major component of the neuroendocrine stress response (Smith and Vale, 2006). This effect has been shown to be mediated through direct stimulation of neurons in the paraventricular nucleus (PVN) of the hypothalamus, leading to the release of corticotropin-releasing factor (CRF) (and vasopressin) that induces secretion of adrenocorticotrophic hormone (ACTH) from the pituitary, which subsequently acts at the adrenal gland to release glucocorticoids into circulation (Lee et al., 2004; Rivier, 2014). It has been suggested that stress may increase motivation to imbibe through synergistic effects on reward circuitry in brain (e.g., mesolimbic dopamine transmission). That is, the activating effects of stress and alcohol on dopamine neurotransmission and on the HPA axis (elevated glucocorticoids) may combine to enhance the rewarding effects of alcohol, thereby facilitating greater propensity to drink (Stephens and Wand, 2012; Uhart and Wand, 2009).
