Eating disorders represent one the most rapidly growing health problems. Abnormal food intake may, in extreme cases, lead to malnutrition or obesity with their attended medical complications. Thus, research concerning the mechanisms governing the cessation of feeding advances our understanding of, and the development of treatments for, eating disorders. Two drugs that are known to suppress food intake, presumably through different mechanisms, are cholecystokinin (CCK), a gut-brain peptide, and d-fenfluramine (DFEN), a serotonin agonist. Using solid food, data reported in the preliminary studies show that the parabrachial nucleus (PBN) is a critical central site for the action of these anorectic drugs. Specifically, lesions of the lateral PBN (a component of the central visceral system) abolished the anorexia induced with CCK but not DFEN, whereas lesions of the medial PBN (a part of the central gustatory system) enhanced the anorectic action of DFEN but not CCK. The goal of the proposed experiments is to investigate the pharmacological basis of this double dissociation of function within the PBN. Assessing the method of food presentation, Specific Aim 1 will determine if PBN lesions disrupt the anorectic effect of systemic CCK and DFEN on liquid, as well as solid, food intake. If our expectations are realized, liquid food will be used in all subsequent experiments because it affords a more accurate analysis of ingestive behavior. Using centrally administered selective CCK-A or CCK-B receptor antagonists alone or in combination with peripherally or centrally infused CCK, Specific Aim 2 begins our evaluation of the role of lateral PBN CCK receptors in food intake. Finally, using drugs that modulate the release and postsynaptic action of serotonin, the experiments of Specific Aim 3 will further our understanding of the role of the medial PBN in the anorectic action of systemic DFEN.
| Trifunovic, Radmila; Reilly, Steve (2006) Medial parabrachial nucleus neurons modulate d-fenfluramine-induced anorexia through 5HT2C receptors. Brain Res 1067:170-6 |
