CB₁ cannabinoid receptor‐mediated modulation of food intake in mice

Abstract

1 Marijuana's appetite-increasing effects have long been known. Recent research suggests that the CB 1 cannabinoid receptor antagonist SR141716A may suppress appetite. This study represents a further, systematic investigation of the role of CB 1 cannabinoid receptors in the pharmacological effects of cannabinoids on food intake. 2 Mice were food-restricted for 24 h and then allowed access to their regular rodent chow for 1 h. Whereas the CB 1 antagonist SR141716A dose-dependently decreased food consumption at doses that did not affect motor activity, D 9 -tetrahydrocannabinol (D 9 -THC) increased food consumption at doses that had no effect on motor activity. O-3259 and O-3257, structural analogs of SR141716A, produced effects similar to those of the parent compound. 3 Amphetamine (a known anorectic) and diazepam (a benzodiazepine and CNS depressant) decreased food consumption, but only at doses that also increased or decreased motor activity, respectively. The CB 2 cannabinoid receptor antagonist SR144528 and the nonpsychoactive cannabinoid cannabidiol did not affect food intake nor activity. 4 SR141716A decreased feeding in wild-type mice, but lacked pharmacological activity in CB 1 knockout mice; however, basal food intake was lower in CB 1 knockout mice. Amphetamine decreased feeding in both mouse genotypes. 5 These results suggest that SR141716A may affect the actions of endogenous cannabinoids in regulating appetite or that it may have effects of its own aside from antagonism of cannabinoid effects (e.g., decreased feeding behavior and locomotor stimulation). In either case, these results strongly suggest that CB 1 receptors may play a role in regulation of feeding behavior.

Cannabinoids enhance gastric X/A-like cells activity.

“…The hyperphagic action was observed also following administration of endocannabinoids: anandamide and 2-AG [32,33,34]. The increase of food intake was observed after systemic and central injection of endocannabinoids and their action was also reversed by CB1 receptors antagonist [10,15,33]. The involvement of CB1 receptors in the regulation of feeding behavior was confirmed by the administration of the selective CB1 receptor antagonist, SR141716 [15,31].…”

“…Both central and peripheral sites of action may be involved [10]. Recently it has been indicated that the effect of endogenous cannabinoids on appetite is mediated by vagal afferent neurons, suggesting a role in modulating gut -brain signaling [11,12].…”

The Novel Cannabinoid CB1 Receptor Neutral Antagonist AM4113 Suppresses Food Intake and Food-Reinforced Behavior but Does not Induce Signs of Nausea in Rats

“…SR141716 attenuated the hyperphagia induced by CB1 agonists (Jamshidi and Taylor, 2001;Kirkham et al, 2002;Williams and Kirkham, 1999), and when administered alone it reduced food intake in a number of different animal models (Arnone et al, 1997;Colombo et al, 1998;Simiand et al, 1998;Williams and Kirkham, 1999). Feeding suppression induced by CB1 antagonists/inverse agonists has been demonstrated in both satiated and food-deprived animals following systemic or central administration, and after either acute or chronic treatment (Chen et al, 2004;Colombo et al, 1998;Shearman et al, 2003;Wiley et al, 2005). Although it is clear that drugs that interfere with CB1 transmission can suppress food intake, the mechanisms by which they accomplish this are less well understood.…”

Peripherally acting CB1-receptor antagonist: the relative importance of central and peripheral CB1 receptors in adiposity control

“…21 Seven to eight-week-old male C57BL/6 mice were fed regular rodent chow (Agribrand Purina 38057). Mice were maintained on a reverse light/dark cycle (light on 2300 to 1100, light off 1100 to 2300) with one animal per cage for a minimum of 7 days before testing.…”