Medial nucleus tractus solitarius oxytocin receptor signaling and food intake control: the role of gastrointestinal satiation signal processing.
Central oxytocin (OT) administration reduces food intake and its effects are mediated, in part, by hindbrain oxytocin receptor (OT-R) signaling. The neural substrate and mechanisms mediating the intake inhibitory effects of hindbrain OT-R signaling are undefined. We examined the hypothesis that hindbrain OT-R-mediated feeding inhibition results from an interaction between medial nucleus tractus solitarius (mNTS) OT-R signaling and the processing of gastrointestinal (GI) satiation signals by neurons of the mNTS. Here, we demonstrated that mNTS or fourth ventricle (4V) microinjections of OT in rats reduced chow intake in a dose-dependent manner. To examine whether the intake suppressive effects of mNTS OT-R signaling is mediated by GI signal processing, rats were injected with OT to the 4V (1 μg) or mNTS (0.3 μg), followed by self-ingestion of a nutrient preload, where either treatment was designed to be without effect on chow intake. Results showed that the combination of mNTS OT-R signaling and GI signaling processing by preload ingestion reduced chow intake significantly and to a greater extent than either stimulus alone. Using enzyme immunoassay, endogenous OT content in mNTS-enriched dorsal vagal complex (DVC) in response to ingestion of nutrient preload was measured. Results revealed that preload ingestion significantly elevated endogenous DVC OT content. Taken together, these findings provide evidence that mNTS neurons are a site of action for hindbrain OT-R signaling in food intake control and that the intake inhibitory effects of hindbrain mNTS OT-R signaling are mediated by interactions with GI satiation signal processing by mNTS neurons.
Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania ongz@sas.upenn.edu.
Zhi Yi
ZY
Ong
Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania.
Amber L
AL
Alhadeff
Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania.
Harvey J
HJ
Grill
D000818:Animals; D004435:Eating / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism*; D012527:Satiation / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D017552:Solitary Nucleus / Q000378:metabolism*
D018045:Receptors, Oxytocin; C588222:oxytocin receptor, rat
energy balance; hindbrain; nucleus tractus solitarius; oxytocin; satiation