Oleamide administered into the nucleus accumbens shell regulates feeding behaviour via CB1 and 5-HT2C receptors

Abstract

The central nervous system control of food intake has been extensively studied, hence, several neurotransmitter systems regulating this function are now clearly identified, for example, the endocannabinoid and serotoninergic systems. The former stimulates feeding while the latter inhibits it. Oleamide (Ole) is a cannabimimetic molecule affecting both systems. In this work, we tested the orexigenic and anorectic potential of Ole when administered into the nucleus accumbens shell (NAcS), a brain region that has been related to the orexigenic effects of cannabinoids. Additionally, we tested if Ole administered into this nucleus affects the activity of the hypothalamic nuclei involved in feeding behaviour, just as other cannabinoids do. We found a hyperphagic effect of Ole that is mediated through CB1 activation. The combination of Ole and the CB1 antagonist, AM251, produced a hypophagia that was fully blocked by SB212084, a 5-HT2C receptor antagonist. We also show that blockade of 5-HT2C and 5-HT2A receptors in the NAcS stimulates food intake. Finally, the combination of Ole and AM251 activates hypothalamic nuclei, an effect also blocked by SB242084. In conclusion, we show, for the first time, that Ole administered into the NAcS has a dual effect on feeding behaviour, acting through cannabinoid and serotonin receptors. These effects probably result from a downstream interaction with the hypothalamus.

Cerebral Markers of the Serotonergic System in Rat Models of Obesity and After Roux‐en‐Y Gastric Bypass

“…In contrast, 5‐HT 4 receptor antagonism in the NAc using RS39604 induces hyperphagia in fed but not food‐deprived mice (7). In addition, intra‐accumbal application of the 5‐HT 2A/2C receptor antagonist ketanserin stimulates food intake in rats (30). Thus, although the association between the 5‐HT system and feeding regulation previously has focused largely on homeostatic regulation in the hypothalamus (31), there is evidence for a role of these receptors in regulating reward aspects of feeding behavior, which results from the present study supports.…”

Selective serotonin receptor stimulation of the medial nucleus accumbens differentially affects appetitive motivation for food on a progressive ratio schedule of reinforcement

“…The current experiments add to a growing literature that suggests that serotonergic signaling within the nucleus accumbens serves important and diverse roles in food-directed motivation [15, 23, 34, 35, 41]. Previous research has suggested that the hypophagic actions of systemic serotonergic agonists are primarily mediated by actions on hypothalamic circuitry involved in the homeostatic regulation of energy balance, with secondary actions on hindbrain circuitry involved in the sensory evaluation of foods [8, 20, 28, 29].…”

ENP11, a potential CB1R antagonist, induces anorexia in rats

“…Due to the fact that extensive scientific literature has supported the endocannabinoid system (eCBs) as a food ingestion modulator, the phyto and synthetic cannabinoids seem to be useful to affect such a function (Koch, 2001;Martínez-González et al, 2004;Méndez-Díaz et al, 2012;Merroun et al, 2009;Pérez-Morales et al, 2012;Soria-Gómez et al, 2010). In this context, it is now known that CB1R antagonists reduce food intake thereby promoting weight loss.…”