ROLE OF BRAINSTEM CRH IN INTAKE AND BODY WEIGHT CONTROL

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

An appreciation of the actions and interactions of a number of neuropeptides is essential for the development of effective pharmacological approaches to feeding disorders and obesity. Mounting evidence suggests that the corticotropin releasing hormone (CRH) system, best known for its role in stress reactions, is an important contributor to feeding and body weight control under normal conditions. The problem addressed in the proposal concerns the central location of the CRH receptors relevant to energy homeostasis. Researchers have tended to focus almost exclusively on hypothalamic structures, despite the fact that CRH neurons and receptors are widely distributed. The proposed experiments evaluate functional contributions of CRH receptors within the caudal brainstem. Urocortin, a CRH agonist, will be delivered to the lateral (forebrain) and fourth (brainstem) ventricles, and to two structures (dorsal vagal complex and parabrachial nucleus) in the brainstem. We will evaluate treatment effects: (1) on short- and long- term intake and body weight, (2) on a set of blood plasma parameters relevant to energy homeostasis including metabolic fuels (glucose, free fatty acids), hormones controlling energy storage and utilization (insulin, glucagon), and correlates of activity in the hypothalamo-pituitary axis (ACTH, corticosterone) and the sympathetic nervous system (epinephrine, norepinephrine), (3) Fos-like immunoreactivity and (4) in chronic decerebrate rats in which neural connections between hypothalamic and brainstem components of the CRH system have been eliminated.