An orexigenic role for mu-opioid receptors in the lateral parabrachial nucleus.
The pontine parabrachial nucleus (PBN) has been implicated in regulating ingestion and contains opioids that promote feeding elsewhere in the brain. We tested the actions of the selective mu-opioid receptor (mu-OR) agonist [d-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) in the PBN on feeding in male rats with free access to food. Infusing DAMGO (0.5-4.0 nmol/0.5 microl) into the lateral parabrachial region (LPBN) increased food intake. The hyperphagic effect was anatomically specific to infusions within the LPBN, dose and time related, and selective for ingestion of chow compared with (nonnutritive) kaolin. The nonselective opioid antagonist naloxone (0.1-10.0 nmol intra-PBN) antagonized DAMGO-induced feeding, with complete blockade by 1.0 nmol and no effect on baseline. The highly selective mu-opioid antagonist d-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 1.0 nmol) also prevented this action of DAMGO, but the kappa-antagonist nor-binaltorphimine did not. Naloxone and CTAP (10.0 nmol) decreased intake during scheduled feeding. Thus stimulating mu-ORs in the LPBN increases feeding, whereas antagonizing these sites inhibits feeding. Together, our results implicate mu-ORs in the LPBN in the normal regulation of food intake.
Wilson
John D
JD
Dept. of Pharmacology and Physiology, Drexel Univ. College of Medicine, Mailstop 488, 245 N. 15th St., Philadelphia, PA 19102-1192, USA.
Nicklous
Danielle M
DM
Aloyo
Vincent J
VJ
Simansky
Kenny J
KJ
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004435:Eating / Q000187:drug effects / Q000502:physiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005508:Food Deprivation / Q000502:physiology; D006963:Hyperphagia / Q000139:chemically induced; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology; D011149:Pons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013004:Somatostatin
D000701:Analgesics, Opioid; C529311:CTAP octapeptide; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D010455:Peptides; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D013004:Somatostatin