Abstract
The protein β-arrestin (βarr) 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. βarr2 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. βarr2 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 βarr2 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 βarr2 modulates behavioral responses to drugs of abuse, as well as its potential as a therapeutic target.
Footnotes
- Received February 7, 2017.
- Accepted March 15, 2017.
This research was supported by the National Institutes of Health National Institute on Drug Abuse [R01 DA038453 (to D.W.)] and the National Institutes of Health National Institute of Neurological Disorders and Stroke [F32 NS098615 (to K.A.P.-S.)].
- Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics
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