Involvement of the opioid system in the orexigenic and hedonic effects of melanin-concentrating hormone

Abstract

Melanin-concentrating hormone (MCH) exerts an orexigenic effect that resembles that of opioids, suggesting that the MCH and opioid systems could interact in controlling the food intake behavior. Three series of experiments were conducted in male Wistar rats: 1) to test the ability of the κ-, μ-, and δ-opioid receptor antagonists binaltorphimine (nor-BNI-κ), β-funaltrexamine (β-FNA-μ), and naltrindole (NTI-δ), respectively, to block the stimulating effects of MCH on food intake; 2) to verify the ability of MCH to induce a positive hedonic response to a sweet stimulus when injected into the nucleus accumbens shell (NAcSh) or right lateral ventricle (LV) of the brain; and 3) to assess the ability of nor-BNI, β-FNA, and NTI to block the effects of MCH on the hedonic response to a sweet stimulus. Nor-BNI, NTI (0, 10 and 40 nmol), and β-FNA (0, 10 and 50 nmol) were administered into the LV prior to injecting MCH (2.0 nmol). To assess the hedonic response, rats were implanted with an intraoral cannula allowing for the infusion of a sweet solution into the oral cavity. Food intake was assessed in sated rats during the first 3 h following the MCH or vehicle (i.e., artificial cerebrospinal fluid) injection. The hedonic response to a sweet stimulus was assessed by examining facial mimics, following the intraoral administration of a sucrose solution. Blockade of each of the three opioid receptors by selective antagonists prevented MCH-induced feeding. Furthermore, MCH-injections into the NAcSh and right LV resulted in enhanced hedonic responses. Finally, antagonism of the three opioid receptors blunted the LV-injected, MCH-induced, facial-liking expressions in response to an intraoral sweet stimulus. Overall, the present study provides evidence to link the MCH and opioid systems in the food intake behavior.