BackgroundExtensive studies have been performed on the role of monoaminergic neuronal systems in rodents exposed to social defeat stress as adults. In the present study, we investigated the role of monoaminergic neuronal systems in the impairment of social behaviors induced by social defeat stress exposure as juveniles.MethodsJuvenile, male C57BL/6J mice were exposed to social defeat stress for 10 consecutive days. From 1 day after the last stress exposure, desipramine, sertraline, and aripiprazole were administered for 15 days. Social behaviors were assessed at 1 and 15 days after the last stress exposure. Monoamine turnover was determined in specific regions of the brain in the mice exposed to the stress.ResultsStress exposure as juveniles induced the impairment of social behaviors in adolescent mice. In mice that showed impairment of social behaviors, turnover of serotonin and dopamine, but not noradrenaline, was decreased in specific brain regions. Acute and repeated administration of desipramine, sertraline, and aripiprazole failed to attenuate the impairment of social behaviors, whereas repeated administration of a combination of sertraline and aripiprazole showed additive attenuating effects.ConclusionsThese findings suggest that social defeat stress exposure as juveniles induces the treatment-resistant impairment of social behaviors in adolescents through dysfunction in the serotonergic and dopaminergic neuronal systems. The combination of sertraline and aripiprazole may be used as a new treatment strategy for treatment-resistant stress-related psychiatric disorders in adolescents with adverse juvenile experiences.

ABSTRACT. This study was performed to investigate the effects of isoprothiolane on cell growth and the production of interleukin (IL)-1 and IL-6 by bovine mammary epithelial cells in vitro. Isoprothiolane increased proliferation of mammary epithelial cells in a dosedependent manner at the concentration of 0.05 to 5 µM when cultured either with or without serum-supplemented medium. In contrast, isoprothiolane (0.0005-5 µM) significantly inhibited the production of IL-1 and IL-6 by mammary epithelial cells. Moreover, the cytokines, IL-1α, IL-1β, IL-6, and tumor necrosis factor (TNF)-α tended to inhibit the proliferation of mammary epithelial cells in a dosedependent manner. These results indicated that isoprothiolane regulated mammary epithelial cell growth in vitro possibly by modulating the production of cytokines.-KEY WORDS: cytokine, isoprothiolane, mammary gland.