While stressful experiences are a part of everyone's life, they can also exact a major toll on health. Stressful life experiences are associated with increased substance abuse, and there exists significant co-morbidity between mental illness and substance use disorders [N.D. Volkow & T.K. Li (2004) Nat. Rev. Neurosci., 5, 963–970; G. Koob & M.J. Kreek (2007) Am. J. Psych., 164, 1149–1159; R. Sinha (2008) Annals N.Y. Acad. Sci., 1141, 105–130]. The risk for development of mood or anxiety disorders after stress is positively associated with the risk for substance use disorders [R. Sinha (2008) Annals N.Y. Acad. Sci., 1141, 105–130], suggesting that there are common substrates for vulnerability to addictive and affective disorders. Understanding the molecular and physiological substrates of stress may lead to improved therapeutic interventions for the treatment of substance use disorders and mental illnesses.