Impact of Dietary Restriction and Exercise on Dopamine Transporter Function in Male and Female Adolescent and Adult Rats
Authors: Owens William Anthony , Gilman T. Lee , George Christina M. , Metzel Lauren M. , Daws Lynette C. 
Published: November 2023

Eating disorders, including anorexia, are a major public health concern, compounded by a lack of effective treatments. They are complex illnesses and their etiology remains unclear, however, dysregulation of dopamine (DA) neurotransmission is a consistent finding. The DA transporter (DAT) terminates DA neurotransmission by high‐affinity uptake of DA into neurons and because of this, is a primary regulator of both the strength and duration of DA signaling. Surprisingly, however, few studies have investigated the relationship between DAT and eating disorders. We and others have shown that DAT activity is highly sensitive to diet. An important caveat of these studies is that they have been performed almost exclusively in adult, male rodents; however eating disorders are more prevalent in adolescents and more so in girls than boys. Here we use a modified version of the activity‐based anorexia (ABA) model to investigate the impact of age, gender, exercise and restricted food access on DAT function to gain insight into the potential role of aberrant DAT activity in eating disorders.

Male and female Sprague‐Dawley rats aged 30 days (post‐natal (P); adolescent) or P90 (adult) at the start of experiments were placed into one of four conditions, free‐access to food/locked running wheel (cage control, C); free‐access to food and running wheel (exercise control, EX), 1‐hour access to food/locked running wheel (food restriction control (FR) or 1‐hour access to food and free access to running wheel (ABA). During this time body weight of FR and ABA rats, regardless of age or gender, decreased markedly. As expected, wheel running/day in ABA rats increased with time, whereas wheel running/day remained constant in EX rats. Notably, wheel running increased more in ABA females than in males and to a dramatically greater extent in adolescent than in adult rats.

As an index of DAT function we used high‐speed chronoamperometry to measure clearance of DA in striatum of anesthetized rats. Maximal velocity (Vmax) for DA clearance was significantly faster in male and female adolescent C and EX rats compared to their adult counterparts. As expected, FR markedly reduced Vmax in both genders and ages. A more complex picture emerged in ABA rats where in adolescent rats, Vmax (relative to C counterparts) was decreased in males, but not in females. In adults, the converse occurred, where both EX and ABA increased Vmax for DA clearance in males, but not in females.

To obtain a behavioral readout of DAT activity, we examined cocaine‐induced locomotion. In both male and female adolescent rats, there were marked leftward shifts in the dose‐response for FR and ABA groups. In contrast, preliminary studies suggest no effect of condition on locomotor response to cocaine in adults.

Together these data reveal a complex relationship between age, gender, exercise, dietary restriction and DAT function. However, in general, adolescents appear to be more susceptible to the impact of dietary restriction and exercise than adults. These preliminary findings help pave the way for future studies investigating the role of DAT in anorexia and as a potential therapeutic target in the treatment of eating disorders.

Support or Funding Information

DA038504 (LCD)