title: MC4-R signaling within the nucleus accumbens shell, but not the lateral hypothalamus, modulates ethanol palatability in rats.
abstract: The Melanocortin (MC) system is one of the crucial neuropeptidergic systems that modulate energy balance. The roles of endogenous MC and MC-4 receptor (MC4-R) signaling within the hypothalamus in the control of homeostatic aspects of feeding are well established. Additional evidence points to a key role for the central MC system in ethanol consumption. Recently, we have shown that nucleus accumbens (NAc), but not lateral hypothalamic (LH), infusion of a selective MC4-R agonist decreases ethanol consumption. Given that MC signaling might contribute to non-homeostatic aspects of feeding within limbic circuits, we assessed here whether MC4-R signaling within the NAc and the lateral hypothalamus (LH) alters normal ingestive hedonic and/or aversive responses to ethanol in rats as measured by a taste reactivity test. Adult male Sprague-Dawley rats were given NAc- or LH- bilateral infusion of the selective MC4-R agonist cyclo (NH-CH(2)-CH(2)-CO-His-D-Phe-Arg-Trp-Glu)-NH(2) (0, 0.75 or 1.5μg/0.5μl/site) and following 30 min, the animals received 1 ml of ethanol solution (6% w/v) intraoral for 1 minute and aversive and hedonic behaviors were recorded. We found that NAc-, but not LH-administration, of a selective MC4-R agonist decreased total duration of hedonic reactions and significantly increased aversive reactions relative to saline-infused animals which support the hypothesis that MC signaling within the NAc may contribute to ethanol consumption by modulating non-homeostatic aspects (palatability) of intake.
authors.affiliation: Departamento de Neurociencia y Ciencias de la Salud, Universidad de Almería, Almería, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Lerma-Cabrera
authors.forename: Francisca
authors.initials: F
authors.lastname: Carvajal
authors.forename: Gabriela
authors.initials: G
authors.lastname: Chotro
authors.forename: Mirari
authors.initials: M
authors.lastname: Gaztañaga
authors.forename: Montserrat
authors.initials: M
authors.lastname: Navarro
authors.forename: Todd E
authors.initials: TE
authors.lastname: Thiele
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Cubero
mesh_terms: D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D055697:Taste Perception / Q000187:drug effects / Q000502:physiology*
chemical_list: D010456:Peptides, Cyclic; D044105:Receptor, Melanocortin, Type 4; C581396:cyclo(NH-CH(2)-CH(2)-CO-His-D-Phe-Arg-Trp-Glu)-NH(2)