Appetitive behavior:                                                                                                          EFA Home
                                                                                                                                                                                                NIH Home
                                                                                                                                                                                                   

     

 Endocannabinoids enhance appetite in animals, and delta(9)-tetrahydrocannabinol, is an approved appetite-enhancing drug. The CB(1) cannabinoid receptor antagonist SR141716A blocks the effects on feeding by endocannabinoids. Berry E, Mechoulam R. Tetrahydrocannabinol and endocannabinoids in feeding and appetite. Pharmacol Ther 2002 Aug;95(2):185

By contrast, hypothalamic 2-AG declined as animals ate. 2-AG injected into the nucleus accumbens shell potently, and dose-dependently, stimulated feeding. This effect was attenuated by the CB1 receptor antagonist SR141716. Kirkham TC, Williams CM, Fasting increased levels of anandamide and 2-AG in the limbic forebrain and 2-AG in the hypothalamus.  Fezza F, Di Marzo V.

   Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol. The hypothalamus regulates visceral processes (e.g., food intake, thermoregulation and control of anterior pituitary secretion)in part with endocannabinoids and CB(1) receptors. Br J Wenger T, Moldrich G. Endocannabinoids stimulate food intake, and the CB(1) receptor antagonist SR141716 reduces food intake. Pharmacol 2002 Jun;136(4):550-7

Prostaglandins Leukot Essent Fatty Acids and anandamide selectively stimulated feeding, with a marked reduction in latency. Apart from its rapid onset, cannabinoid-induced eating retained the normal, species-typical sequence, characteristic of untreated, free-feeding rats. Our data suggest that exogenously administered cannabinoids promote eating by increasing the incentive value of food and support a role for endocannabinoids in the regulation of the appetitive aspects of feeding motivation. Williams CM, Kirkham. The role of endocannabinoids in the hypothalamic regulation of visceral function. TC. 2002 Feb;66(2-3):301-7 Both Delta(9)-THC

   Observational analysis of feeding induced by Delta(9)-THC and anandamide. The cDNA and genomic sequences encoding G protein-coupled cannabinoid receptors (Cnrs) from several species have now been cloned. Endogenous cannabinoids (endocannabinoids), synthetic and hydrolyzing enzymes and transporters that define neurochemically-specific cannabinoid brain pathways have been identified. Endocannabinoid lipid signaling molecules alter activity at G protein-coupled receptors (GPCR) and possibly at anandamide-gated ion channels, such as vanilloid receptors. Onaivi ES, Leonard CM, Ishiguro H, Zhang PW, Lin Z, Akinshola BE, Uhl GR. Endocannabinoids and cannabinoid receptor genetics. Prog Neurobiol 2002 Apr;66(5):307-44.  Physiol Behav 2002 Jun;76(2): 241-250.

   Pretreatment with the selective CB1 cannabinoid antagonist SR 141716 (30 microg x 0.5 microl(-1)), 30 min prior to anandamide injection resulted in an attenuation of the anandamide-induced hyperphagia (P<0.001). Jamshidi N, Taylor DA.> Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats. To date, studies using CB1 knockout mice have supported the possible role of endocannabinoids in retrograde synaptic inhibition in the hippocampus, in long-term potentiation and memory, in the development of opiate dependence, and in the control of appetite and food intake. They also suggested the existence of as yet unidentified cannabinoid receptors in the cardiovascular and central nervous systems. The use of CB2 receptor knockout mice suggested a role for this receptor in macrophage-mediated helper T cell activation. Novel physiologic functions of endocannabinoids as revealed through the use of mutant mice. Kunos G, Batkai S. Neurochem Res 2001 Sep;26 (8-9):1015-21. Br J Pharmacol 2001 Nov;134(6):1151-4

   Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance. Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides, such as alpha-melanocyte-stimulating hormone, and downregulating orexigenic (appetite-stimulating) factors, primarily neuropeptide Y. Defective leptin signalling is associated with elevated hypothalamic, but not cerebellar, levels of endocannabinoids in obese db/db and ob/ob mice and Zucker rats. Acute leptin treatment of normal rats and ob/ob mice reduces anandamide and 2-arachidonoyl glycerol in the hypothalamus. These findings indicate that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin. Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z, Fezza F, Miura GI, Palmiter RD, Sugiura T, Kunos G.

   Leptin-regulated endocannabinoids are involved in maintaining food intake. Neither naloxone nor SR141716 reliably affected feeding when administered alone. By contrast, combining the two antagonists significantly suppressed chow intake. The data reveal a synergistic interaction and provide further evidence of important functional relationships between endogenous cannabinoid and opioid systems. Kirkham TC, Williams CM. Synergistic efects of opioid and cannabinoid antagonists on food intake. Psychopharmacology (Berl) 2001 Jan 1;153(2):267-270. Nature 2001 Apr 12;410(6830):822-5 Comment in: Nature. 2001 Apr 12;410(6830):763, 765.