A role for neuropeptide-Y, dynorphin, and noradrenaline in the central control of food intake after food deprivation.
A marked increase in food intake is observed in the rat after central injection of neuropeptide-Y (NPY), dynorphin, or noradrenaline (NA). Levels of both NPY and dynorphin are increased in the hypothalamus of food-deprived rats. The aim of this study was to explore the role of NPY, dynorphin, and NA in the central control of feeding after a period of food deprivation. We have investigated the effect of intracerebroventricular injection of a monoclonal antibody to NPY (NPYAb), a potent and selective kappa-opioid receptor antagonist norbinaltorphimine (norBNI), and the alpha-adrenergic antagonist phentolamine on fast-induced food intake. In animals provided with food after a 24-h fast, NPYAb given 10 min before presentation of food reduced food intake by 30% (P < 0.01) compared to that of animals pretreated with an antibody to chloroquine. A similar (34%; P < 0.05) reduction in fast-induced feeding occurred after pretreatment with norBNI. If norBNI was given together with NPYAb, then a reduction of 51% (P < 0.05) was observed. Pretreatment with phentolamine reduced fast-induced food intake by 39% (P < 0.05), with no evidence of an additive effect when phentolamine was given together with NPYAb. These data would support a role for endogenous NPY, dynorphin, and NA in the mediation of fast-induced feeding. NPY would seem to act independently of dynorphin, but through the same mechanism as NA.
Lambert
P D
PD
Division of Endocrinology and Metabolism, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Wilding
J P
JP
al-Dokhayel
A A
AA
Bohuon
C
C
Comoy
E
E
Gilbey
S G
SG
Bloom
S R
SR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D004399:Dynorphins / Q000502:physiology*; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D005508:Food Deprivation / Q000502:physiology*; D007116:Immunization, Passive; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009478:Neuropeptide Y / Q000276:immunology / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D009478:Neuropeptide Y; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D004399:Dynorphins; D009638:Norepinephrine; D010646:Phentolamine