Orexin A in the rostrolateral hypothalamic area induces feeding by modulating GABAergic transmission

A. J. Thorpe, D. F. Doane, D. C. Sweet, J. L. Beverly, C. M. Kotz

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The neuromodulatory peptides orexin A and B are important central nervous system regulators of appetite. We previously identified the rostral lateral portion of the hypothalamus as an area important to orexin A feeding regulation. As γ-aminobutyric-acid (GABA) within the lateral hypothalamus also mediates feeding, we sought to determine the relationship between orexin and GABA signaling within this site. Adult male Sprague-Dawley rats were implanted with cannulae directed to the rostral lateral hypothalamus and saclofen (GABA-B receptor antagonist), biccuculine (GABA-A receptor antagonist) or muscimol (GABA-A receptor agonist) were injected prior to orexin A. Both GABA antagonists failed to significantly affect orexin A-induced feeding, but muscimol significantly and dose dependently inhibited orexin A-induced feeding. Using in vivo microdialysis GABA release within this region significantly dropped during the first hour following orexin A administration, coinciding with orexin A-induced feeding. Together, these data indicate that orexin A may influence food intake by decreasing GABAergic tone within the rostral lateral hypothalamus.

Original languageEnglish (US)
Pages (from-to)60-66
Number of pages7
JournalBrain Research
Volume1125
Issue number1
DOIs
StatePublished - Dec 13 2006

Keywords

  • 2-Hydroxysaclofen
  • Bicuculline
  • Feeding behavior
  • Hypocretin
  • Microdialysis
  • Muscimol

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