Food Restriction and Reward in Rats

Food restriction is a defining characteristic of anorexia nervosa and a risk factor for binge pathology. Basic research related to drug addiction indicates that food restriction increases drug reward magnitude, persistence of preference for a drug-paired environment, and relapse to drug seeking. These phenomena suggest that drugs of abuse subvert the adaptive mechanisms that normally facilitate foraging, learning, and ingestion when food is scarce. Similarly, if supranormally rewarding, energy-dense food is abundant but the physiological effects of underfeeding prevail due to restricted intake, the risk of developing maladaptive addiction-like eating behavior may increase. In this chapter, methods are described for assessing neurotransmitter receptor mechanisms and intracellular signaling pathways in the nucleus accumbens (NAc) that contribute to enhanced reward sensitivity in food-restricted rats. These methods combine intracerebral drug microinjection with the curve-shift rate-frequency protocol of intracranial self-stimulation testing. The addition of continuous intraventricular infusion of metabolic hormone or feeding-related neuropeptide receptor ligands is described as a means of assessing peripheral responses that may be antecedents to central nervous system changes of interest. When these studies are guided by biochemical findings in the NAc of food-restricted rats, the approach enables identification of neuroadaptations that increase reward sensitivity and suggests others that may increase synaptic plasticity and ingrain behavior. The goal is to generate a set of defined candidate mechanisms that can be evaluated for their involvement in the development and maintenance of disordered eating.