Social defeat in adolescent mice increases vulnerability to alcohol consumption

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.This work was supported by the following research grants: Ministerio de Ciencia e Innovación, (SAF2011-23420) to Jorge Manzanares; Ministerio de Economía y Competitividad, Dirección General de Investigación (PSI2011-24762) to Jose Miñarro; Generalidad Valenciana, Consejería de Educación (PROMETEO/2009/072) to Jose Miñarro; and Instituto de Salud ‘Carlos III’ (FIS), Redes Telemáticas de Investigación Cooperativa en Salud (RETICS), Red de Trastornos Adictivos (RTA), fondos FEDER (RD06/0001/1004, RD12/0028/0019 to Jorge Manzanares; and RD06/001/0016, RD12/0028/005 to Jose Miñarro).Peer reviewe