Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors

Abstract

SR 141716, a selective central CB1 cannabinoid receptor antagonist, markedly and selectively reduces sucrose feeding and drinking as well as neuropeptide Y-induced sucrose drinking in rats. SR 141716 also decreases ethanol consumption in C57BL/6 mice. In contrast, blockade of CB1 receptors only marginally affects regular chow intake or water drinking. The active doses of SR 141716 (0.3-3 mg/kg) are in the range known to antagonize the characteristic effects induced by cannabinoid receptor agonists. These results suggest for the first time that endogenous cannabinoid systems may modulate the appetitive value of sucrose and ethanol, perhaps by affecting the activity of brain reward systems.

Nicotine-Associated Cues Maintain Nicotine-Seeking Behavior in Rats Several Weeks after Nicotine Withdrawal: Reversal by the Cannabinoid (CB1) Receptor Antagonist, Rimonabant (SR141716)

“…The lack of effects of rimonabant on the inactive lever presses is of limited use in providing a conclusive control for motor artifacts because of the low response rates. However, at this dose, the drug did not produce any gross behavioral effects (Arnone et al, 1997), suggesting that the reduction of conditioned responding did not result from nonspecific (motor) deleterious effects. In addition, it has been reported that rimonabant did not affect operant responding for food (Navarro et al, 2001), or a 10% sucrose solution (De Vries et al, 2001) or cocaine injections (Fattore et al, 1999), suggesting that it did not affect the reward system per se.…”

“…Pretreatment with the cannabinoid CB 1 receptor antagonist rimonabant (SR141716; Rinaldi-Carmona et al, 1994) reduced nicotine, ethanol, methamphetamine, and morphine self-administration in rodents (Arnone et al, 1997;Navarro et al, 2001;Cohen et al, 2002;Vinklerova et al, 2002). Rimonabant also blocked the acquisition of conditioned place preference induced by morphine and cocaine (Chaperon et al, 1998).…”

Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions

“…11,[23][24][25] Although the molecular basis and cellular basis for the action of inverse agonists have been well documented and the physiological endpoints are well defined, the detailed physiological mechanisms through which modulation of CB1R translate to changes in peripheral tissue metabolism can be difficult to dissect. The following sections will address the physiological MOA related to the site of action for inverse agonists and the physiological pathways involved.…”

“…72,73 In addition, food intake studies showed that rimonabant inhibited the intake of both regular chow or palatable food. 24,74,75 Tetrahydrocannabinol (THC) has also been shown to stimulate the intake of either chow or highfat sweetened diet. 76 These data generally support a model in which CB1R inverse agonists reduce the intake of all macronutrients with no selectivity related to palatability.…”

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

“…Anandamide is capable of increasing food intake in rats [87], while the antagonist SR-141716A inhibits the intake of food [88][89][90] and is currently being evaluated as an anti-obesity treatment with good results (see below). The underlying circuitry responsible for the therapeutic efficacy of cannabinoids in stimulating appetite is not yet known, although it is probably related to the fact that the CB1 receptor, anandamide, and 2-AG are present in the hypothalamus, which is known to be associated with feeding [91].…”