Arresting the Development of Addiction: The Role of β-Arrestin 2 in Drug Abuse

The protein beta-arrestin (beta arr) 2 directly interacts with receptors and signaling pathways that mediate the behavioral effects of drugs of abuse, making it a prime candidate for therapeutic interventions. beta arr2 drives desensitization and internalization of G protein-coupled receptors, including dopamine, opioid, and cannabinoid receptors, and it can also trigger G protein-independent intracellular signaling. barr2 mediates several drug-induced behaviors, but the relationship is complex and dependent on the type of behavior (e.g., psychomotor versus reward), the class of drug (e.g., psychostimulant versus opioid), and the circuit being interrogated (e.g., brain region, cell type, and specific receptor ligand). Here we discuss the current state of research concerning the contribution of beta arr2 to the psychomotor and rewarding effects of addictive drugs. Next we identify key knowledge gaps and suggest new tools and approaches needed to further elucidate the neuroanatomical substrates and neurobiological mechanisms to explain how barr2 modulates behavioral responses to drugs of abuse, as well as its potential as a therapeutic target.