Role of Ghrelin in the Induction of Anxiogenic Behavior

Barnard College, New York NY

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Abstract

DESCRIPTION (provided by applicant): The recent identification of the orexigenic gut-brain peptide ghrelin has led to a rapid investigation of this peptide's physiologic function specifically in relation to its role in the hypothalamic control of feeding and energy homeostasis. However, to date little is known about other centrally mediated behavioral effects of ghrelin including its involvement in the induction of anxiogenic behavior. While very recent data imply that hypothalamic ghrelin mediates behavioral responses to stress, possibly associated with its orexigenic action, direct tests of this hypothesis have yet to be conducted, and anatomical sites of action within hypothalamic nuclei remain to be identified. An initial experiment will determine the effects of ghrelin on anxiogenic behaviors in the rat assessed using an elevated plus maze, a standard tool used in the evaluation of anxiety and emotional behavior. The aim will be to identify sites within the hypothalamus mediating ghrelin's effects on anxiety. Specific sites within the hypothalamus under investigation include the arcuate nucleus, dorsomedial nucleus, lateral perifornical hypothalamus, paraventricular nucleus and the ventromedial nucleus. A subsequent study will assess ghrelin's role in feeding motivation and simultaneously measure several stress-like behaviors including oral stereotypies, wet dog shakes and excessive levels of grooming behavior. Similar anatomical sites will be investigated in order to provide additional evidence of hypothalamic mediation. A final experiment is designed to determine whether ghrelin's involvement in anxiogenic and feeding behaviors is mediated via a corticotropin releasing hormone (CRH) mechanism. This will be accomplished by pretreating animals with a CRH receptor antagonist prior to ghrelin treatment. Any alteration in anxiogenic and feeding behaviors would support such an interaction. The overall objective of the proposed work is to enhance our understanding of emotional and motivational processes through an examination of ghrelin's potential involvement in the induction of anxiety and feeding motivation.