title: Increased vulnerability to ethanol consumption in adolescent maternal separated mice.
abstract: The purpose of this study was to evaluate the effects of early life stress on the vulnerability to ethanol consumption in adolescence. To this aim, mice were separated from their mothers for 12 hours/day on postnatal days 8 and 12. Emotional behavior (light-dark box, elevated plus maze and tail suspension tests) and pre-attentional deficit (pre-pulse inhibition) were evaluated in adolescent maternal separated (MS) mice. Alterations of the corticotropin-releasing factor (CRF), glucocorticoid receptor (NR3C1), tyrosine hydroxylase (TH), mu-opioid receptor (MOr), brain-derived neurotrophic factor (BDNF), neuronal nuclei (NeuN), microtubule-associated protein 2 (MAP2) and neurofilament heavy (NF200)-immunoreactive fibers were studied in the paraventricular nucleus of the hypothalamus (PVN), ventral tegmental area (VTA), nucleus accumbens (NAc) or hippocampus (HIP). The effects of maternal separation (alone or in combination with additional stressful stimuli) on ethanol consumption during adolescence were evaluated using the oral ethanol self-administration paradigm. MS mice presented mood-related alterations and pre-attentional deficit. Increased CRF, MOr and TH, and reduced BDNF, NR3C1, NeuN, MAP2 and NF200-immunoreactive fibers were observed in the PVN, NAc and HIP of adolescent MS mice. In the oral ethanol self-administration test, adolescent MS mice presented higher ethanol consumption and motivation. Exposure to additional new stressful stimuli during adolescence significantly increased the vulnerability to ethanol consumption induced by maternal separation. These results clearly demonstrated that exposure to early life stress increased the vulnerability to ethanol consumption, potentiated the effects of stressful stimuli exposure during adolescence on ethanol consumption and modified the expression of key targets involved in the response to stress, ethanol reinforcing properties and cognitive processes.
authors.affiliation: Instituto de Neurociencias, Campus de San Juan, Universidad Miguel Hernández-CSIC, Spain.|Red Temática de Investigación Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, MICINN and FEDER, Spain.
authors.forename: María S
authors.initials: MS
authors.lastname: García-Gutiérrez
authors.affiliation: Instituto de Neurociencias, Campus de San Juan, Universidad Miguel Hernández-CSIC, Spain.|Red Temática de Investigación Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, MICINN and FEDER, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Navarrete
authors.affiliation: Instituto de Neurociencias, Campus de San Juan, Universidad Miguel Hernández-CSIC, Spain.|Red Temática de Investigación Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, MICINN and FEDER, Spain.
authors.forename: Auxiliadora
authors.initials: A
authors.lastname: Aracil
authors.affiliation: Instituto de Neurociencias, Campus de San Juan, Universidad Miguel Hernández-CSIC, Spain.
authors.forename: Adrián
authors.initials: A
authors.lastname: Bartoll
authors.affiliation: Department of Psychiatry, School of Medicine, Complutense University, Spain.|Instituto de Investigación Hospital 12 de Octubre, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Martínez-Gras
authors.affiliation: Neurosciences Division, Center for Applied Medical Research (CIMA), University of Navarra, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Lanciego
authors.affiliation: Red Temática de Investigación Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, MICINN and FEDER, Spain.|Department of Psychiatry, School of Medicine, Complutense University, Spain.|Instituto de Investigación Hospital 12 de Octubre, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rubio
authors.affiliation: Instituto de Neurociencias, Campus de San Juan, Universidad Miguel Hernández-CSIC, Spain.|Red Temática de Investigación Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, MICINN and FEDER, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Manzanares
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology* / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D008813:Mice, Inbred ICR; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol
keywords: Adolescence; alcohol use disorders; gene expression; maternal separation; mood disorders; response to stress