Corticostriatal contributions to dysregulated motivated behaviors in stress, depression, and substance use disorders.

Coordinated network activity, particularly in circuits arising from the prefrontal cortex innervating the ventral striatum, is crucial for normal processing of reward-related information which is perturbed in several psychiatric disorders characterized by dysregulated reward-related behaviors. Stress-induced depression and substance use disorders (SUDs) both share this common underlying pathology, manifested as deficits in perceived reward in depression, and increased attribution of positive valence to drug-predictive stimuli and dysfunctional cognition in SUDs. Here we review preclinical and clinical data that support dysregulation of motivated and reward-related behaviors as a core phenotype shared between these two disorders. We posit that altered processing of reward-related stimuli arises from dysregulated control of subcortical circuits by upstream regions implicated in executive control. Although multiple circuits are directly involved in reward processing, here we focus specifically on the role of corticostriatal circuit dysregulation. Moreover, we highlight the growing body of evidence indicating that such abnormalities may be due to heightened neuroimmune signaling by microglia, and that targeting the neuroimmune system may be a viable approach to treating this shared symptom.