noladin-ether and Hyperphagia

BACKGROUND AND PURPOSE Endocannabinoid systems are strongly implicated in the physiological control of appetite and eating behaviour, with cannabinoid CB(1) receptor agonists and antagonists, respectively, increasing or decreasing food intake. This study examined the acute actions of the putative endocannabinoid noladin ether on food intake and eating motivation, assessing how it affects the amount of work expended by animals to obtain food. EXPERIMENTAL APPROACH Non-deprived male rats were injected systemically with noladin ether to assess its acute effects on ad libitum feeding of a standard laboratory diet. Additionally, the effects of noladin on lever pressing for palatable food were determined using a progressive ratio (PR) operant paradigm. KEY RESULTS Noladin dose dependently increased 2 h food intake, with a significant effect over 1 h after a dose of 0.5 mg·kg(-1). In the PR test, this hyperphagic dose of noladin ether promoted sustained high rates of responding and significantly increased the total number of lever presses and break-point. These latter effects were prevented by pretreatment with 1.0 mg·kg(-1) of the selective CB(1) antagonist surinabant (SR147778), that alone had no effect on responding. CONCLUSIONS AND IMPLICATIONS This is the first report of hyperphagia induced by acute noladin administration, and the first description of behavioural actions in rats. Consistent with prevailing notions about the role of endocannabinoids in appetite, a hyperphagic dose of noladin markedly increased efforts expended by animals to obtain food. Thus, noladin exerts a specific action on eating motivation; possibly promoting eating by increasing the incentive value of food.

Topics: Animals; Behavior, Animal; Cannabinoid Receptor Modulators; Eating; Endocannabinoids; Glycerides; Hyperphagia; Male; Motivation; Piperidines; Pyrazoles; Rats; Receptor, Cannabinoid, CB1

Stimulation of cannabinoid CB(1) receptors in nucleus accumbens shell has been shown to stimulate feeding and enhance positive 'liking' reactions to intraoral sucrose. This study examined the behavioural effects of noladin ether and 2-arachidonoylglycerol following infusion into accumbens shell, on chow intake and food preference in high-carbohydrate and high-fat preferring rats. Noladin ether, potently and dose-dependently stimulated chow intake as compared with 2-arachidonoylglycerol in free-feeding rats. In the diet preference paradigm, in which rats were given free access to both, high-carbohydrate (HC) and high-fat (HF) diets simultaneously, an intra-accumbens administration of noladin ether as well as 2-arachidonoylglycerol, preferentially enhanced fat consumption over carbohydrate in both HF- and HC-preferring rats. These effects were significantly attenuated by the CB(1) receptor antagonist, AM 251. These results suggesting that, the endocannabinoids through CB(1) receptors, affects appetite for specific dietary components. Both these agents exert a specific action on eating motivation and possibly promoting eating by enhancing the incentive value of food. Altogether these findings reinforce the idea that the endogenous cannabinoid system in the accumbens shell may be important to augment reward-driven feeding via modulation of CB(1) receptor signalling pathways.

Topics: Animals; Appetite; Arachidonic Acids; Cannabinoid Receptor Modulators; Diet; Diet, High-Fat; Dietary Carbohydrates; Eating; Endocannabinoids; Food Preferences; Glycerides; Hyperphagia; Male; Nucleus Accumbens; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Sucrose