Aerobic Exercise Attenuates Reinstatement of Cocaine-Seeking Behavior and Associated Neuroadaptations in the Prefrontal Cortex

Background: Exercise has recently been suggested as an attractive alternative to pharmacotherapy for treating drug addiction. The goal of this study was to determine, using an animal model, whether aerobic exercise may block reinstatement of cocaine-seeking and its underlying neurobiology (i.e., neuronal signaling in the prefrontal cortex). Methods: Following acquisition and 10 days of 24-hour access to cocaine (1.5 mg/kg/infusion) or saline under a discrete trial procedure (four infusions/hr), rats began a 14-day abstinence period. During this period, rats were either given access to a running-wheel for 2-hours each day or placed in similar boxes with the wheel locked. Cocaine-seeking was assessed following the 14th day of abstinence using a within-session extinction/cue-induced reinstatement procedure. Neuronal activity was assessed by examining phosphorylated levels of extracellular signal-regulated kinase (pERK) using Western blot analysis. Results: Wheel running reduced cocaine-seeking during both extinction and reinstatement. Cocaine-seeking was positively associated with pERK levels in the prefrontal cortex. Although pERK levels were not different among saline controls, in the cocaine group, pERK levels were significantly decreased by exercise. Conclusions: Aerobic exercise may reduce relapse vulnerability by preventing the increase in cocaine-seeking and associated neuroadaptations in the prefrontal cortex that develop over an abstinence period.