Activity-based anorexia (ABA), an animal model of anorexia nervosa in which rats are given free access to running wheels but restricted access to food, induces many symptoms of anorexia nervosa. This model has been used to examine biological factors that may contribute to the development of anorexia nervosa. Here, the role of the serotonin (5-HT) system in the development of ABA was examined in female rats.
In Experiment 1, susceptibility to ABA was examined in rats treated with 8-OH-DPAT, a drug that reduces 5-HT neurotransmission. In this and subsequent experiments, rats had free access to running wheels, and food was restricted to 2 h/ day. Daily treatment with 8-OH-DPAT decreased wheel running and weight loss, suggesting that decreased 5-HT activity reduces susceptibility to ABA. In Experiment 2 we determined whether antagonism of the 5-HT2C receptor decreased susceptibility to ABA. Rats were subjected to the ABA paradigm as in Experiment 1 and treated daily with RS-102221, a selective 5-HT2C receptor antagonist. RS-102221 did not affect food intake or wheel running. However, RS-102221 treatment slowed weight loss, suggesting that antagonism of the 5-HT2C receptor decreases susceptibility to ABA. Because RS-102221 did not affect food intake and wheel running, some other mechanism, such as a change in thermoregulation, must mediate these results. In Experiment 3, neuronal activation in response to fenfluramine, a 5-HT agonist, was examined in rats with ABA. Rats were allowed to lose 0, 10, or 25% of their baseline body weight in the ABA paradigm. After reaching the weight loss criterion, rats were injected with fenfluramine or saline vehicle. Two h later, rats were perfused and brains were collected and processed for c-Fos-like immunoreactivity. Weight loss interacted with fenfluramine treatment to increase c-Fos expression in the nucleus of the solitary tract. Weight loss alone increased c-Fos expression in the arcuate nucleus, and fenfluramine treatment alone increased c-Fos expression in the central nucleus of the amygdala. This suggests that brain regions important in the control of energy balance are affected by exposure to the ABA paradigm. Taken together, these data suggest that 5-HT plays an important role in the development of ABA.