AgRP neurons coordinate the mitigation of activity-based anorexia

Anorexia nervosa (AN) is a debilitating and deadly disease characterized by low body mass index due to diminished food intake, and oftentimes concurrent hyperactivity. A high percentage of AN behavioral and metabolic phenotypes can be replicated in rodents given access to a voluntary running wheel and subject to food restriction, termed activity-based anorexia (ABA). Despite the well-documented body weight loss observed in AN human patients and ABA rodents, much less is understood regarding the neurobiological underpinnings of these maladaptive behaviors. Moreover, while exercise has been shown to diminish the activity of hunger-promoting hypothalamic agouti-related peptide (AgRP) neurons, much less is known regarding their activity and function in the mediation of food intake during ABA. Here, feeding microstructure analysis revealed ABA mice decreased food intake due to increased interpellet interval retrieval and diminished meal number. Longitudinal activity recordings of AgRP neurons in ABA animals revealed a maladaptive inhibitory response to food. We then demonstrated that ABA development or progression can be mitigated by chemogenetic AgRP activation through the reprioritization of food intake (increased meal number) over hyperactivity. These results elucidate a potential neural target for the amelioration of behavioral maladaptations present in AN patients.

Developmental Analysis of Schedule-Induced Polydipsia

In a developmental analysis of schedule-induced polydipsia (SIP), 8 female, albino rats were exposed to either a FI-60-sec. or a VI-60-sec. reinforcement schedule with 4 Ss in each group. Results indicated that the adventitious reinforcement explanation for SIP is not tenable, since licks did not occur with equal probability in all periods of the interpellet interval during SIP development; lick bursts coming in contact with pellet deliveries were a result rather than a cause of SIP; and SIP developed more slowly on the VI than on the FI schedule.