Thioperamide, a histamine H3 receptor antagonist, powerfully suppresses peptide YY-induced food intake in rats

Biol Psychiatry. 1999 Feb 15;45(4):475-81. doi: 10.1016/s0006-3223(98)00044-4.

Abstract

Background: Whether or not peptide YY (PYY)-induced hyperphagia is modified by the histaminergic system in the brain is not yet known.

Methods: We investigated the effect on feeding of intracerebroventricular (ICV) administration of a specific histamine H3 receptor antagonist prior to ICV administration of PYY in rats.

Results: PYY (1, 3, and 10 micrograms/10 microL) strongly induced feeding behavior in a dose-dependent manner in sated rats. The 4-hour food intake induced by 3 micrograms/10 microL of PYY was equal to that induced by a 16-hour fast. The ICV administration of thioperamide (40.8, 122.4, and 408.5 micrograms/10 microL) did not suppress the 4-hour food intake induced by 16-hour fasting; however, thioperamide produced dose-dependent and strong inhibition of hyperphagia induced by a 3-microgram dose of PYY.

Conclusions: These results suggest that the effect of PYY on appetite is different than that induced by fasting and may involve a histaminergic mechanism.

MeSH terms

  • Analysis of Variance
  • Animals
  • Appetite Regulation / drug effects
  • Appetite Regulation / physiology
  • Bulimia / physiopathology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drinking / drug effects
  • Eating / drug effects*
  • Fasting / physiology
  • Histamine Antagonists / pharmacology*
  • Hyperphagia / chemically induced
  • Hyperphagia / physiopathology
  • Injections, Intraventricular
  • Male
  • Peptide YY / drug effects*
  • Piperidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Histamine H3 / physiology*
  • Satiation / drug effects
  • Time Factors

Substances

  • Histamine Antagonists
  • Piperidines
  • Receptors, Histamine H3
  • Peptide YY
  • thioperamide