Orexin A in the rostrolateral hypothalamic area induces feeding by modulating GABAergic transmission.
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 gamma-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.
Thorpe
A J
AJ
Division of Nutritional Sciences, University of Illinois at Urbana, Champaign, 1207 W. Gregory Dr., Urbana, IL 61801, USA.
Doane
D F
DF
Sweet
D C
DC
Beverly
J L
JL
Kotz
C M
CM
D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009118:Muscimol / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; C057491:2-hydroxysaclofen; D001640:Bicuculline