Brain oxytocin receptor antagonism blunts the effects of anorexigenic treatments in rats: evidence for central oxytocin inhibition of food intake.
The inhibition of food intake in rats that results from various anorexigenic treatments is frequently associated with pituitary secretion of oxytocin (OT), but is not caused by circulating OT. We, therefore, evaluated the potential role of brain OT in mediating anorexia induced in rats by systemic administration of cholecystokinin (CCK), hypertonic saline (HS), or lithium chloride (LiCl), treatments that are known to stimulate pituitary OT secretion as well as to inhibit food intake. Food intake was analyzed in 22-h food-deprived rats pretreated with icv injections of either artificial cerebrospinal fluid (aCSF) or 9 nmol of an OT receptor antagonist, [d(CH2)5, Tyr(OMe)2,Orn8]vasotocin (OVT), which was the dose found to be most effective to antagonize the anorexia induced by CCK and HS. Pretreatment with the OT receptor antagonist icv significantly blunted the anorexigenic effect of each agent. After CCK (10 micrograms/kg, ip), food intake increased from 28 +/- 5% of basal intake after a CSF icv to 48 +/- 8% after OVT icv (P less than 0.01); after HS (2 ml 2 M NaCl, ip), food intake increased from 9 +/- 4% of basal intake after aCSF icv to 43 +/- 7% after OVT icv (P less than 0.01); and after LiCl (1.125 mmol/kg, ip), food intake increased from 55 +/- 4% of basal intake after a CSF icv to 80 +/- 9% after OVT icv (P less than 0.01). These data support the hypothesis that pituitary secretion of OT after anorexigenic treatments in rats is associated with coactivation of centrally projecting brain OT pathways, some of which are causally related to the induced inhibition of food intake.
Olson
B R
BR
Department of Medicine, University of Pittsburgh, Pennsylvania 15261.
Drutarosky
M D
MD
Stricker
E M
EM
Verbalis
J G
JG
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001921:Brain / Q000502:physiology*; D002712:Chlorides / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008297:Male; D010121:Oxytocin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018045:Receptors, Oxytocin; D012462:Saline Solution, Hypertonic / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D002712:Chlorides; D018045:Receptors, Oxytocin; D012462:Saline Solution, Hypertonic; D010121:Oxytocin; C042951:oxytocin,1-(beta-mercapto-(beta, beta-cyclopentamethylene)propionic acid)-Tyr(OMe)(2)-Orn(8)-; D002766:Cholecystokinin; D008094:Lithium; D018021:Lithium Chloride