Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: Stimulation of eating by 2-arachidonoyl glycerol

Tim C. Kirkham, Claire M. Williams, Filomena Fezza, Vincenzo Di Marzo

Research output: Contribution to journalArticle

Abstract

1. Endocannabinoids are implicated in appetite and body weight regulation. In rodents, anandamide stimulates eating by actions at central CB1 receptors, and hypothalamic endocannabinoids may be under the negative control of leptin. However, changes to brain endocannabinoid levels in direct relation to feeding or changing nutritional status have not been investigated. 2. We measured anandamide and 2-arachidonoyl glycerol (2-AG) levels in feeding-associated brain regions of rats, during fasting, feeding of a palatable food, or after satiation. Endocannabinoid levels were compared to those in rats fed ad libitum, at a point in their daily cycle when motivation to eat was absent. Fasting increased levels of anandamide and 2-AG in the limbic forebrain and, to a lesser extent, of 2-AG in the hypothalamus. By contrast, hypothalamic 2-AG declined as animals ate. No changes were detected in satiated rats. Endocannabinoid levels in the cerebellum, a control region not directly involved in the control of food intake, were unaffected by any manipulation. 3. As 2-AG was most sensitive to variation during feeding, and to leptin regulation in a previous study, we examined the behavioural effects of 2-AG when injected into the nucleus accumbens shell, a limbic forebrain area strongly linked to eating motivation. 2-AG potently, and dose-dependently, stimulated feeding. This effect was attenuated by the CB1 receptor antagonist SR141716. 4. These findings provide the first direct evidence of altered brain levels of endocannabinoids, and of 2-AG in particular, during fasting and feeding. The nature of these effects supports a role for endocannabinoids in the control of appetitive motivation.

Original languageEnglish
Pages (from-to)550-557
Number of pages8
JournalBritish Journal of Pharmacology
Volume136
Issue number4
Publication statusPublished - 2002

Fingerprint

Satiation
Endocannabinoids
Prosencephalon
Hypothalamus
Fasting
Eating
Motivation
Cannabinoid Receptor CB1
rimonabant
Leptin
Brain
2-arachidonylglycerol
Nucleus Accumbens
Appetite
Nutritional Status
Cerebellum
Rodentia
Body Weight
Food

Keywords

  • 2-arachidonoyl glycerol
  • Anandamide
  • Appetite
  • Cannabinoid
  • Nucleus accumbens
  • SR141716

ASJC Scopus subject areas

  • Pharmacology

Cite this

Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation : Stimulation of eating by 2-arachidonoyl glycerol. / Kirkham, Tim C.; Williams, Claire M.; Fezza, Filomena; Di Marzo, Vincenzo.

In: British Journal of Pharmacology, Vol. 136, No. 4, 2002, p. 550-557.

Research output: Contribution to journalArticle

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AB - 1. Endocannabinoids are implicated in appetite and body weight regulation. In rodents, anandamide stimulates eating by actions at central CB1 receptors, and hypothalamic endocannabinoids may be under the negative control of leptin. However, changes to brain endocannabinoid levels in direct relation to feeding or changing nutritional status have not been investigated. 2. We measured anandamide and 2-arachidonoyl glycerol (2-AG) levels in feeding-associated brain regions of rats, during fasting, feeding of a palatable food, or after satiation. Endocannabinoid levels were compared to those in rats fed ad libitum, at a point in their daily cycle when motivation to eat was absent. Fasting increased levels of anandamide and 2-AG in the limbic forebrain and, to a lesser extent, of 2-AG in the hypothalamus. By contrast, hypothalamic 2-AG declined as animals ate. No changes were detected in satiated rats. Endocannabinoid levels in the cerebellum, a control region not directly involved in the control of food intake, were unaffected by any manipulation. 3. As 2-AG was most sensitive to variation during feeding, and to leptin regulation in a previous study, we examined the behavioural effects of 2-AG when injected into the nucleus accumbens shell, a limbic forebrain area strongly linked to eating motivation. 2-AG potently, and dose-dependently, stimulated feeding. This effect was attenuated by the CB1 receptor antagonist SR141716. 4. These findings provide the first direct evidence of altered brain levels of endocannabinoids, and of 2-AG in particular, during fasting and feeding. The nature of these effects supports a role for endocannabinoids in the control of appetitive motivation.

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