Cortico-striatal circuits: Novel therapeutic targets for substance use disorders

It is widely believed that substance use disorder (SUD) results from both pre-alterations (vulnerability) and/or post-alterations (drug effects) on cortico-striatal circuits. These circuits are essential for cognitive control, motivation, reward dependent learning, and emotional processing. As such, dysfunctions in cortico-striatal circuits are thought to relate to the core features of SUD, which include compulsive drug use, loss of the ability to control drug intake, and the emergence of negative emotional states (Koob and Volkow, 2010. Neuropsychopharmacology 35(1), 217-238). While the brain circuits underlying SUD have been studied in human patients largely through imaging studies, experiments in animals have allowed researchers to examine the specific cell-types within these circuits to reveal their role in behavior relevant to SUD. Here, we will review imaging studies on cortico-striatal systems that are altered in SUD, and describe animal experiments that relate SUD to specific neural projections and cell types within this circuitry. We will end with a discussion of novel clinical approaches such as deep brain stimulation (DBS), repeated transcranial magnetic stimulation (rTMS), and pharmacological targeting of G protein-coupled receptor (GPCR) heteromers that may provide promising avenues for modulating these circuits to combat SUD in humans.