The two most prevalent substance use disorders involve alcohol and nicotine, which are often co-abused. Robust preclinical and translational evidence indicates that individuals initiate drug use for the acute rewarding effects of the substance. The development of negative emotional states is key for the transition from recreational use to substance use disorders as subjects seek the substance to obtain relief from the negative emotional states of acute withdrawal and protracted abstinence. The neuropeptide corticotropin-releasing factor (CRF) is a major regulator of the brain stress system and key in the development of negative affective states. The present review examines the role of CRF in preclinical models of alcohol and nicotine abuse and explores links between CRF and anxiety-like, dysphoria-like, and other negative affective states. Finally, the present review discusses preclinical models of nicotine and alcohol use with regard to the CRF system, advances in molecular and genetic manipulations of CRF, and the importance of examining both males and females in this field of research.
Keywords: Anxiety; Extended amygdala; Neuropeptide; Sex differences; Stress; Substance use disorder.
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