Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol
Open accessAbstract
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. 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. 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. 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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Administration of 2AG into the shell of the nucleus accumbens increases food intake.
“Furthermore, administration of 2AG into the shell of the nucleus accumbens, an extra-hypothalamic area strongly linked to eating motivation increases food intake (Kirkham et al., 2002).”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Kirkham et al., 2002
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- Authors
- Kirkham, T. C., Williams, C. M., Fezza, F., & Marzo, V. D.
- Affiliations
- University of Reading (GB)
- Istituto di Chimica Biomolecolare (IT)
- Corresponding author
- Kirkham, Tim C
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2002-06
- Volume
- 136
- Issue
- 4
- Pages
- 550-557
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1573386
- OpenAlex
- W1963482720
- Cited by
- 788
- References
- 57
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 17 · 2023: 17 · 2022: 18 · 2021: 34 · 2020: 20 · 2019: 32 · 2018: 34 · 2017: 33 · 2016: 23 · 2015: 37 · 2014: 32 · 2013: 25 · 2012: 34
- FWCI
- 15.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Directorate for Biological Sciences
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- endocannabinoids, 2-arachidonoylglycerol, anandamide, appetite regulation, feeding behavior, fasting, satiation, hypothalamus, limbic forebrain, nucleus accumbens shell, CB1 receptor, SR141716, leptin, eating motivation, palatable food
- MeSH terms
- Animals, Arachidonic Acids, Fasting, Feeding Behavior, Glycerides, Hypothalamus, Limbic System, Male, Satiation, Rats, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids
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