title: Adolescent binge-like ethanol exposure reduces basal α-MSH expression in the hypothalamus and the amygdala of adult rats.
abstract: Melanocortins (MC) are central peptides that have been implicated in the modulation of ethanol consumption. There is experimental evidence that chronic ethanol exposure reduces α-MSH expression in the limbic and hypothalamic brain regions and alters central pro-opiomelanocortin (POMC) mRNA activity in adult rats. Adolescence is a critical developmental period of high vulnerability in which ethanol exposure alters corticotropin releasing factor, neuropeptide Y, substance P and neurokinin neuropeptide activities, all of which have key roles in ethanol consumption. Given the involvement of MC and the endogenous inverse agonist AgRP in ethanol drinking, here we evaluate whether a binge-like pattern of ethanol treatment during adolescence has a relevant impact on basal and/or ethanol-stimulated α-MSH and AgRP activities during adulthood. To this end, adolescent Sprague-Dawley rats (beginning at PND25) were pre-treated with either saline (SP group) or binge-like ethanol exposure (BEP group; 3.0 g/kg given in intraperitoneal (i.p.) injections) of one injection per day over two consecutive days, followed by 2 days without injections, repeated for a total of 8 injections. Following 25 ethanol-free days, we evaluated α-MSH and AgRP immunoreactivity (IR) in the limbic and hypothalamic nuclei of adult rats (PND63) in response to ethanol (1.5 or 3.0 g/kgi.p.) and saline. We found that binge-like ethanol exposure during adolescence significantly reduced basal α-MSH IR in the central nucleus of the amygdala (CeA), the arcuate nucleus (Arc) and the paraventricular nucleus of the hypothalamus (PVN) during adulthood. Additionally, acute ethanol elicited AgRP IR in the Arc. Rats given the adolescent ethanol treatment required higher doses of ethanol than saline-treated rats to express AgRP. In light of previous evidence that endogenous MC and AgRP regulate ethanol intake through MC-receptor signaling, we speculate that the α-MSH and AgRP disturbances induced by binge-like ethanol exposure during adolescence may contribute to excessive ethanol consumption during adulthood.
authors.affiliation: Departamento de Neurociencia y Ciencias de la Salud, Universidad de Almería, Almería 04120, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Lerma-Cabrera
authors.forename: Francisca
authors.initials: F
authors.lastname: Carvajal
authors.forename: Manuel
authors.initials: M
authors.lastname: Alcaraz-Iborra
authors.forename: Leticia
authors.initials: L
authors.lastname: de la Fuente
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: D000367:Age Factors; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000521:alpha-MSH / Q000378:metabolism*
chemical_list: D000431:Ethanol; D000521:alpha-MSH
keywords: AA Alko; ANA Alko; Adolescents; AgRP; AgRP immunoreactivity; Arc; BEC; BEP; BNST; BW; Binge-like ethanol; CRF; CeA; DMH; HPA; IHC; IR; LH; MC; MC receptors; MC-R; MTII; NAc; P; PC1/3; PND; POMC; PVN; SP; VMH; VTA; agouti-related peptide; alcohol rats; alcohol-preferring rats; bed nucleus of the stria terminalis; binge-like ethanol pre-treatment group; blood ethanol concentration; body weight; central nucleus of amygdala; corticotropin releasing factor; dorsomedial nucleus of the hypothalamus; hypothalamic arcuate nucleus; hypothalamic–pituitary–adrenal axis; immunohistochemistry; immunoreactivity; lateral hypothalamus; melanocortin; melanotan-II; non alcohol rats; nucleus accumbens; paraventricular nucleus of the hypothalamus; postnatal day; pro-hormone convertase 1/3; pro-opiomelanocortin; saline pre-treatment group; ventral tegmental area; ventromedial nucleus of the hypothalamus; α-MSH; α-melanocyte stimulating hormone; β-MSH; β-melanocyte stimulating hormone; γ-MSH; γ-melanocyte stimulating hormone