Exploring Cortical Interneurons in Substance Use Disorder: From Mechanisms to Therapeutic Perspectives.

Interneurons (INs) play a crucial role in the regulation of neural activity within the medial prefrontal cortex (mPFC), a brain region critically involved in executive functions and behavioral control. In recent preclinical studies, dysregulation of INs in the mPFC has been implicated in the pathophysiology of substance use disorder, characterized by vulnerability to chronic drug use. Here, we explore the diversity of mPFC INs and their connectivity and roles in vulnerability to addiction. We also discuss how these INs change over time with drug exposure. Finally, we focus on noninvasive brain stimulation as a therapeutic approach for targeting INs in substance use disorder, highlighting its potential to restore neural circuits.