This Article Full Text Full Text (PDF) All Versions of this Article: 146/9/3724    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ford, G. K. Articles by Jessop, D. S. Search for Related Content PubMed PubMed Citation Articles by Ford, G. K. Articles by Jessop, D. S. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Stress

Orexin Expression and Function: Glucocorticoid Manipulation, Stress, and Feeding Studies

Henry Wellcome Laboratory for Integrative Neuroscience and Endocrinology (G.K.F., M.S.H., D.S.J.), University of Bristol, Bristol BS1 3NY, United Kingdom; Department of Biology (D.N.C.J.), Psychiatry Centre of Excellence for Drug Discovery (CEDD) and Discovery Research (S.W.), GlaxoSmithKline, Harlow Essex CM19 5AW, United Kingdom; Metabolic Diseases (K.A.A.-B.), Metabolic and Viral Diseases CEDD, GlaxoSmithKline, Research Triangle Park, North Carolina 27709

Address all correspondence and requests for reprints to: Dr. M. Harbuz, Henry Wellcome Laboratory for Integrative Neuroscience and Endocrinology, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, United Kingdom. E-mail: m.s.harbuz{at}bris.ac.uk.

We investigated the effects of glucocorticoid manipulation on orexin-A-induced feeding and prepro-orexin mRNA levels in the lateral hypothalamic area (LHA) of the rat brain. Adrenalectomy (ADX) reduced orexin-A-induced feeding over 4 h by about 60%, compared with shams, an effect that was reversed by corticosterone (CORT) replacement. ADX had no effect on prepro-orexin mRNA levels in the LHA in either the morning or the evening; however, message was up-regulated by CORT in the morning but not the evening. An increased number of emulsion grains per cell in the LHA suggests that this is a specific increase in prepro-orexin mRNA and is not due to an increased number of cells expressing message. Prepro-orexin mRNA levels in the LHA were elevated 4 h after injection of lipopolysaccharide, compared with saline-injected controls. Partial but not complete abolition of orexin-A-induced feeding by ADX suggests that orexin-A-induced feeding may be mediated through glucocorticoid-dependent and glucocorticoid-independent pathways. In the morning increased prepro-orexin mRNA after CORT replacement demonstrates that orexin expression is sensitive to increased concentrations of glucocorticoids. However, the lack of effect of ADX on prepro-orexin mRNA levels suggests that endogenous glucocorticoids are not involved in tonic regulation of basal prepro-orexin expression. Overall our data constitute a body of evidence for an integrated relationship between central orexin expression, stress, glucocorticoid manipulation, and feeding patterns in the rat.