The role of histamine 3 receptors in the control of food intake in a seasonal model of obesity

the Siberian hamster

Preeti H. Jethwa, Perry Barrett, Yvonne Duffton Turnbull, Rachel A. Enright, Amy Warner, Michelle Murphy, Francis J. P. Ebling

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Siberian hamsters develop hypophagia and increase catabolism of fat reserves in response to short photoperiods resulting in a natural loss of body weight in winter. We previously found that histamine 3 receptor (H3R) mRNA in the posterior hypothalamus is significantly decreased in short photoperiods. We hypothesized that this lower expression of H3R might contribute to the winter hypophagic state, therefore we examined the effects of the H3R agonist imetit and inverse agonists clobenpropit and thioperamide on food intake. We expressed the Siberian hamster H3R receptor in vitro and confirmed that imetit, clobenpropit and thioperamide are bound specifically, thus validating them as tools to investigate the role of H3R in vivo. Intracerebroventricular administration of histamine decreased food intake in hamsters in the fat summer state. Administration of imetit to hamsters in the lean state increased food intake, whereas administration of inverse agonists decreased food intake, though this was associated with decreased locomotor activity. Both H3R inverse agonists prevented the nocturnal rise in body temperature indicating additional effects on energy expenditure. In summary, our results suggest that increased availability of central histamine or the reduction of H3R activity decrease food intake. These effects are similar to those observed in hamsters in short photoperiods. Behavioural Pharmacology 20:155-165 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Original languageEnglish
Pages (from-to)155-165
Number of pages11
JournalBehavioural Pharmacology
Volume20
Issue number2
DOIs
Publication statusPublished - Mar 2009

Keywords

  • agonist and inverse agonist
  • body temperature
  • clobenpropit
  • food intake
  • histamine
  • histamine 3 receptor
  • imetit
  • locomotor activity
  • thioperamide
  • H-3 receptors
  • brain histamine
  • body-weight
  • H3 receptor
  • rat
  • antagonist
  • expression
  • mice
  • pharmacology
  • food intake

Cite this

The role of histamine 3 receptors in the control of food intake in a seasonal model of obesity : the Siberian hamster. / Jethwa, Preeti H.; Barrett, Perry; Turnbull, Yvonne Duffton; Enright, Rachel A.; Warner, Amy; Murphy, Michelle; Ebling, Francis J. P.

In: Behavioural Pharmacology, Vol. 20, No. 2, 03.2009, p. 155-165.

Research output: Contribution to journalArticle

Jethwa, Preeti H. ; Barrett, Perry ; Turnbull, Yvonne Duffton ; Enright, Rachel A. ; Warner, Amy ; Murphy, Michelle ; Ebling, Francis J. P. / The role of histamine 3 receptors in the control of food intake in a seasonal model of obesity : the Siberian hamster. In: Behavioural Pharmacology. 2009 ; Vol. 20, No. 2. pp. 155-165.
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abstract = "Siberian hamsters develop hypophagia and increase catabolism of fat reserves in response to short photoperiods resulting in a natural loss of body weight in winter. We previously found that histamine 3 receptor (H3R) mRNA in the posterior hypothalamus is significantly decreased in short photoperiods. We hypothesized that this lower expression of H3R might contribute to the winter hypophagic state, therefore we examined the effects of the H3R agonist imetit and inverse agonists clobenpropit and thioperamide on food intake. We expressed the Siberian hamster H3R receptor in vitro and confirmed that imetit, clobenpropit and thioperamide are bound specifically, thus validating them as tools to investigate the role of H3R in vivo. Intracerebroventricular administration of histamine decreased food intake in hamsters in the fat summer state. Administration of imetit to hamsters in the lean state increased food intake, whereas administration of inverse agonists decreased food intake, though this was associated with decreased locomotor activity. Both H3R inverse agonists prevented the nocturnal rise in body temperature indicating additional effects on energy expenditure. In summary, our results suggest that increased availability of central histamine or the reduction of H3R activity decrease food intake. These effects are similar to those observed in hamsters in short photoperiods. Behavioural Pharmacology 20:155-165 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.",
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AB - Siberian hamsters develop hypophagia and increase catabolism of fat reserves in response to short photoperiods resulting in a natural loss of body weight in winter. We previously found that histamine 3 receptor (H3R) mRNA in the posterior hypothalamus is significantly decreased in short photoperiods. We hypothesized that this lower expression of H3R might contribute to the winter hypophagic state, therefore we examined the effects of the H3R agonist imetit and inverse agonists clobenpropit and thioperamide on food intake. We expressed the Siberian hamster H3R receptor in vitro and confirmed that imetit, clobenpropit and thioperamide are bound specifically, thus validating them as tools to investigate the role of H3R in vivo. Intracerebroventricular administration of histamine decreased food intake in hamsters in the fat summer state. Administration of imetit to hamsters in the lean state increased food intake, whereas administration of inverse agonists decreased food intake, though this was associated with decreased locomotor activity. Both H3R inverse agonists prevented the nocturnal rise in body temperature indicating additional effects on energy expenditure. In summary, our results suggest that increased availability of central histamine or the reduction of H3R activity decrease food intake. These effects are similar to those observed in hamsters in short photoperiods. Behavioural Pharmacology 20:155-165 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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