Dopaminergic Perturbations from Food Restriction and Exercise are Sex‐Dependently Amplified During Adolescence

Eating disorders, which are 2.5‐fold more prevalent in females than males, typically emerge during adolescence. Afflicting at least 3 percent of teenagers, eating disorders such as anorexia nervosa, bulimia nervosa, and binge eating disorder entail severe health consequences in addition to their psychological toll. Yet no effective treatments for eating disorders exist. An established regulator of both eating behaviors and physical activity, the dopaminergic system undergoes a sensitive maturation period during adolescence. However, studies into the role of the dopaminergic system in ontogeny of eating disorders are lacking, as are investigations into dopaminergic system maturation in adolescent females. Here we measured function of the dopamine transporter (DAT), a critical regulator of dopaminergic signaling, using both in vivo high‐speed chronoamperometry and locomotor assays of acute cocaine response. Employing an activity‐based anorexia paradigm for 4–5 days, we investigated how food restriction, free exercise on a running wheel, or the combination thereof impacted DAT function in adult (postnatal day 90) and adolescent (postnatal day 30) Sprague‐Dawley rats of both sexes. Food restriction alone or with exercise in adolescent rats of both sexes produced leftward shifts in the dose‐response to the locomotor‐promoting effects of cocaine, though the maximal response to cocaine was blunted in females within these two groups. In adults, only food restricted females exhibited a significant increase in maximal cocaine‐induced locomotor response. Clearance of dopamine in dorsal striatum was not significantly altered by food restriction and/or exercise in adults. In contrast, food restriction plus exercise significantly attenuated dopamine clearance in adolescent males, and food restriction alone or combined with exercise elicited pronounced dopamine clearance reductions in adolescent females. Together, these findings suggest that adolescent plasticity of the dopaminergic system confers – particularly in females – vulnerability to eating disorders and persistence of associated unhealthy behaviors (e.g., compulsive exercise). Therefore, drugs that enhance dopamine uptake or otherwise reduce dopamine signaling duration may prove efficacious in the treatment of emerging adolescent eating disorders. Ongoing experiments are evaluating striatal DAT expression in these animals, and future experiments will focus on optimizing longer term food restriction and exercise conditions in adolescents to facilitate investigation of pharmacologic interventions. Support or Funding Information This research was supported by R21 DA038504 to LCD. TLG is supported by T32 DA031115 to Charles P. France. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .