title: Social defeat in adolescent mice increases vulnerability to alcohol consumption.
abstract: This study employs an oral operant conditioning paradigm to evaluate the effects of repeated social defeat during adolescence on the reinforcing and motivational actions of ethanol in adult OF1 mice. Social interaction, emotional and cognitive behavioral aspects were also analyzed, and real-time polymerase chain reaction (PCR) experiments were performed to study gene expression changes in the mesocorticolimbic and hypothalamus-hypophysis-adrenal (HHA) axis. Social defeat did not alter anxiety-like behavior in the elevated plus maze or cognitive performance in the passive avoidance and Hebb-Williams tests. A social interaction test revealed depression-like symptoms and social subordination behavior in defeated OF1 mice. Interestingly, social defeat in adolescence significantly increased the number of effective responses, ethanol consumption values and motivation to drink. Finally, real-time PCR analyses revealed that social defeat significantly increased tyrosine hydroxylase and corticotropin-releasing hormone in the ventral tegmental area and paraventricular nucleus, respectively. In contrast, mu-opioid receptor gene expression was decreased in the nucleus accumbens of socially defeated mice. In summary, these findings suggest that exposure to social defeat during adolescence increases vulnerability to the rewarding effects of ethanol without affecting emotional or cognitive performance. The gene expression alterations we have observed in the mesocorticolimbic and HHA axis systems of defeated mice could be related with their increased ethanol consumption. These results endorse future research into pharmacological strategies that modulate these systems for the treatment of social stress-related alcohol consumption problems.
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Spain.|Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Rodriguez-Arias
authors.affiliation: Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Spain.|Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Navarrete
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Spain.|Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Spain.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Blanco-Gandia
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Spain.|Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Spain.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Arenas
authors.affiliation: Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Spain.
authors.forename: Adrián
authors.initials: A
authors.lastname: Bartoll-Andrés
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Spain.|Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Aguilar
authors.affiliation: Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Spain.|Unidad de Psiquiatría, Hospital Universitario '12 de Octubre', Spain.|Instituto de Investigación '12 de Octubre', Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rubio
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Spain.|Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Miñarro
authors.affiliation: Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Spain.|Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Manzanares
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D001362:Avoidance Learning; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D003216:Conditioning, Operant; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D003863:Depression / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D000431:Ethanol / Q000008:administration & dosage; D020869:Gene Expression Profiling; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D051379:Mice; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017450:Receptors, Opioid, mu / Q000235:genetics; D012646:Self Administration; D012919:Social Behavior; D013315:Stress, Psychological / Q000235:genetics* / Q000523:psychology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D017450:Receptors, Opioid, mu; D000431:Ethanol; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase
keywords: Anxiety; ethanol; hypothalamus-hypophysis-adrenal axis; memory; mesocorticolimbic system; social defeat