Neural Basis of Ventromedial Hypothalamic Oxytocin-Driven Decrease in Appetite

Neuroscience. 2017 Dec 16;366:54-61. doi: 10.1016/j.neuroscience.2017.10.008. Epub 2017 Oct 14.

Abstract

Objectives: Oxytocin (OT) administration in the ventromedial hypothalamic nucleus (VMH) reduces chow intake. The nature of VMH OT's anorexigenic action remains unclear. Here we provide insight into neural mechanisms underlying VMH OT-driven anorexia by (a) identifying feeding-related brain sites activated by VMH OT injection; (b) measuring VMH OT receptor (OTr) mRNA changes in response to hunger and palatability; and (c) examining how VMH OT affects episodic sweet solution intake in sated and hungry rats.

Method: We established effective doses of VMH OT in deprivation-induced and scheduled feeding and determined whether an OT antagonist blocks the effect. Then, OT (or antagonist) was injected in the VMH of sated rats given episodically sucrose and saccharin solutions. OT was also injected in hungry animals offered simultaneously chow and sugar water. Brain activation after VMH OT was determined by Fos immunoreactivity (IR). OTr expression was established with rtPCR after chow deprivation or saccharin exposure.

Results: VMH OT decreased intake of chow and the effect was reversed by the antagonist, though the antagonist alone was not orexigenic. OT did not affect intakes of energy-dilute saccharin and sucrose solutions in sated or hungry rats. Fos IR was elevated in the VMH and energy balance-related paraventricular and arcuate nuclei, but not reward areas. VMH OTr expression was higher in hungry rats than in sated controls; saccharin intake had no effect.

Conclusion: OT acting in the VMH decreases intake driven by energy not by palatability, and it stimulates activity of hypothalamic sites controlling energy balance.

Keywords: VMH; energy; oxytocin; reward.

MeSH terms

  • Animals
  • Anorexia / chemically induced
  • Appetite Depressants / administration & dosage
  • Appetite*
  • Feeding Behavior*
  • Male
  • Oxytocin / administration & dosage
  • Oxytocin / physiology*
  • Rats, Sprague-Dawley
  • Receptors, Oxytocin / metabolism
  • Saccharin / administration & dosage
  • Sucrose / administration & dosage
  • Ventromedial Hypothalamic Nucleus / drug effects
  • Ventromedial Hypothalamic Nucleus / metabolism
  • Ventromedial Hypothalamic Nucleus / physiology*

Substances

  • Appetite Depressants
  • Receptors, Oxytocin
  • oxytocin receptor, rat
  • Oxytocin
  • Sucrose
  • Saccharin