extra-hypothalamic stress circuitry in the brain. Use of animal (primarily rodent) models has been critical to advancing our understanding about how chronic alcohol-induced changes in neuroendocrine and brain stress systems, particularly those intertwined with reward circuitry, underlie expression of withdrawal symptoms reflective of a negative affective state (i.e., dysphoria, anxiety), along with increased motivation to self-administer alcohol (Figure 1). As highlighted in this review, elevated glucocorticoids, along with activation of several pro-stress neuropeptides (CRF, DYN) and anti-stress neuropeptide systems (nociceptin, NPY, oxytocin) have been shown to play a significant role in these dynamic aspects of the addiction process. Heightened autonomic (sympathomimetic) effects also contribute to the stress, negative emotional, and motivational consequences of chronic alcohol exposure. Future studies aimed at elucidating mechanisms of engagement and timing of these (and other) stress-related systems will be critical in providing a more comprehensive understanding of the dynamic physiological and psychological underpinnings of alcohol addiction. Use of animal models also will be key to identifying new targets and evaluating potential therapeutics for treating problem drinking, particularly stress-related excessive alcohol consumption. This research also has important implications for developing more effective treatments for those individuals presenting with comorbidity of alcohol use disorder and a stress-related
