title: Down-regulation of cannabinoid-1 (CB-1) receptors in specific extrahypothalamic regions of rats with dietary obesity: a role for endogenous cannabinoids in driving appetite for palatable food?
abstract: Agonists at cannabinoid-1 (CB-1) receptors stimulate feeding and particularly enhance the reward aspects of eating. To investigate whether endogenous cannabinoids might influence appetite for palatable food, we compared CB-1 receptor density in the forebrain and hypothalamus, between rats fed standard chow (n=8) and others given palatable food (n=8) for 10 weeks to induce dietary obesity. CB-1 receptor density was significantly decreased by 30-50% (P<0.05) in the hippocampus, cortex, nucleus accumbens and entopeduncular nucleus of diet-fed rats. Furthermore, CB-1 receptor density in the hippocampus, nucleus accumbens and entopeduncular nucleus was significantly inversely correlated with intake of palatable food (r(2)=0.25-0.35; all P<0.05). By contrast, CB-1 receptor binding in the hypothalamus was low and not altered in diet-fed rats. CB-1 receptor down-regulation is consistent with increased activation of these receptors by endogenous cannabinoids. Acting in areas such as the nucleus accumbens and hippocampus, which are involved in the hedonic aspects of eating, cannabinoids may therefore drive appetite for palatable food and thus determine total energy intake and the severity of diet-induced obesity. However, cannabinoids in the hypothalamus do not appear to influence this aspect of eating behaviour.
authors.affiliation: Diabetes Endocrinology Research Group, Department of Medicine, University of Liverpool, Duncan Building, Daulby Street, Liverpool L69 3GA, UK. harrold@liverpool.ac.uk
authors.forename: Joanne A
authors.initials: JA
authors.lastname: Harrold
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Elliott
authors.forename: Peter J
authors.initials: PJ
authors.lastname: King
authors.forename: Peter S
authors.initials: PS
authors.lastname: Widdowson
authors.forename: Gareth
authors.initials: G
authors.lastname: Williams
mesh_terms: D000818:Animals; D001066:Appetite / Q000502:physiology*; D001069:Appetite Regulation / Q000502:physiology; D063385:Cannabinoid Receptor Modulators; D015536:Down-Regulation / Q000502:physiology*; D002149:Energy Intake / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
chemical_list: D063385:Cannabinoid Receptor Modulators; D005231:Fatty Acids, Unsaturated; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug