Motivated behaviors are controlled by the mesocorticolimbic dopamine (DA) system, consisting of projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and prefrontal cortex (PFC), with input from structures including the medial preoptic area (mPOA). Sex differences are present in this circuit, and gonadal hormones (e.g., estradiol and testosterone) are important for regulating DA transmission. Early life stress (ELS) also regulates the mesocorticolimbic DA system. ELS modifies motivated behaviors and the underlying DA circuitry, increasing risk for disorders such as substance use disorder, major depression, and schizophrenia. ELS has been shown to change gonadal hormone signaling in both sexes. Thus, one way that ELS could impact mesocorticolimbic DA is by altering the efficacy of gonadal hormones. This review provides evidence for this idea by integrating the gonadal hormone, motivation, and ELS literature to argue that ELS alters gonadal hormone signaling to impact motivated behavior. We also discuss the importance of these effects in the context of understanding risk and treatments for psychiatric disorders in men and women.
Copyright © 2020. Published by Elsevier Ltd.