A non-peptide oxytocin receptor agonist, WAY-267,464, alleviates novelty-induced hypophagia in mice: Insights into changes in c-Fos immunoreactivity

Pawel K. Olszewski, Christine Ulrich, Nicholas Ling, Kerry Allen, Allen S. Levine

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Anxiety caused by the novelty of food or of the environment where the food is presented leads to suppression of consumption (hyponeophagia) reflected by an increased latency to begin feeding and decreased food intake. Studies suggest that some anxiolytics, mainly benzodiazepines and SSRIs, resolve hyponeophagia. Though the neurohormone oxytocin (OT) affects both anxiety responsiveness and feeding-related homeostasis, the link between OT and hyponeophagia has not been established. The current experiments examined the effect of OT receptor stimulation on hyponeophagia in mice and associated changes in brain activity. We found that the OT receptor agonist, WAY-267,464, at 10 and 30 mg/kg b. wt. IP, reduced the latency to approach food and increased the amount of food eaten in hyponeophagia tests differing in animals' motivation to eat (hunger, reward) and the anxiogenic context of environmental novelty (illumination and type of the cage). This effect was abolished by the pretreatment with the OT receptor antagonist, L-368,899, at 10 mg/kg b. wt. The antagonist also suppressed social transmission of preference for novel food. Mice subjected to novelty conditions causing hypophagia showed significant changes in c-Fos immunoreactivity in the hippocampus, lateral septum, cingulate and piriform cortex and in the bed nucleus of the stria terminalis, lateral division, posterolateral part (STLP). The pretreatment with WAY-267,464 restored c-Fos levels in the STLP to values detected in control animals subjected to non-anxiogenic conditions. We conclude that OT plays a role in shaping the magnitude of the novelty stress-provoked hypophagia and the activity of the relevant neural networks.

Original languageEnglish (US)
Pages (from-to)367-372
Number of pages6
JournalPharmacology Biochemistry and Behavior
Volume124
DOIs
StatePublished - Sep 2014

Bibliographical note

Funding Information:
This research was supported by the Royal Society of New Zealand Marsden ( UOW1203 ) grant. We would like to thank Ayman Aneece for technical assistance.

Keywords

  • Anorexia
  • Neophobia
  • Oxytocin

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