Abstract:
Midbrain dopamine circuits are central for the development and maintenance of substance use disorder. Although the critical role of dopamine has long been known, interventions based on dopamine system modulation have so far largely been ineffective in reducing the burden of substance use disorder. This is likely because the dopamine system is composed of multiple subcircuits that mediate distinct aspects of motivated behavior, including drug-induced behavioral changes. Here we will discuss our recent efforts to dissect the contributions of distinct input cell populations, including from the globus pallidus and bed nucleus of the stria terminalis, in psychostimulant-induced reward and withdrawal behaviors, and how these findings have been used to identify novel small-molecule modulators that can reduce psychostimulant use.