Hindbrain noradrenergic input to the hypothalamic PVN mediates the activation of oxytocinergic neurons induced by the satiety factor oleoylethanolamide.
Oleoylethanolamide (OEA) is a gut-derived endogenous lipid that stimulates vagal fibers to induce satiety. Our previous work has shown that peripherally administered OEA activates c-fos transcription in the nucleus of the solitary tract (NST) and in the paraventricular nucleus (PVN), where it enhances oxytocin (OXY) expression. The anorexigenic action of OEA is prevented by the intracerebroventricular administration of a selective OXY receptor antagonist, suggesting a necessary role of OXYergic mediation of OEA's effect. The NST is the source of direct noradrenergic afferent input to hypothalamic OXY neurons, and therefore, we hypothesized that the activation of this pathway might mediate OEA effects on PVN neurons. To test this hypothesis, we subjected rats to intra-PVN administration of the toxin saporin (DSAP) conjugated to an antibody against dopamine-β-hydroxylase (DBH) to destroy hindbrain noradrenergic neurons. In these rats we evaluated the effects of OEA (10 mg/kg, ip) on feeding behavior, on c-Fos and OXY immunoreactivity in the PVN, and on OXY immunoreactivity in the posterior pituitary gland. We found that the DSAP lesion completely prevented OEA's effects on food intake, on Fos and OXY expression in the PVN, and on OXY immunoreactivity of the posterior pituitary gland; all effects were maintained in sham-operated rats. These results support the hypothesis that noradrenergic NST-PVN projections are involved in the activation of the hypothalamic OXY system, which mediates OEA's prosatiety action.
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy;
Adele
A
Romano
Catarina Soares
CS
Potes
Bianca
B
Tempesta
Tommaso
T
Cassano
Vincenzo
V
Cuomo
Thomas
T
Lutz
Silvana
S
Gaetani
D059331:Adrenergic Neurons / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004299:Dopamine beta-Hydroxylase / Q000276:immunology; D063388:Endocannabinoids; D000922:Immunotoxins / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009829:Oleic Acids / Q000494:pharmacology*; D010121:Oxytocin / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012249:Rhombencephalon / Q000187:drug effects* / Q000502:physiology; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology; D000076985:Saporins; D012527:Satiation / Q000187:drug effects*
D063388:Endocannabinoids; D000922:Immunotoxins; D009829:Oleic Acids; D054789:Ribosome Inactivating Proteins, Type 1; C488250:oleoylethanolamide; D010121:Oxytocin; D004299:Dopamine beta-Hydroxylase; D000076985:Saporins
acylethanolamides; gut-brain axis; neuropeptides; noradrenergic projections; nucleus of solitary tract; paraventricular nucleus