The emerging role of autophagy in the rewarding and stimulant behaviors in models of substance use disorder

Substance use disorder (SUD) is a major worldwide health problem with a historic global high of 316 million people using drugs, representing a 15% rise in prevalence over the previous decade. A comprehensive understanding of the pathophysiology of SUD will enable the development of novel therapeutic strategies to improve patient outcomes. Preclinical research on the neurobiology of SUD primarily focuses on the immediate monoaminergic systems response, changes in gene expression, and long-term maladaptive synaptic and circuit-level alterations as the key pathophysiological mechanisms. A few recent publications point to a novel role for the proteostatic process, autophagy, in the rewarding and stimulant effects in animal models of SUD. In this minireview, we summarize the key findings of these reports and discuss potential future directions. These emerging roles expand our understanding of autophagy in the nervous system-from a housekeeping recycling process to a multifunctional regulator of signal transduction, neurotransmission, and behavior-and suggest that autophagy may be a novel therapeutic target in SUD.