Eszopiclone facilitation of the antidepressant efficacy of fluoxetine using a social defeat stress model

This study analyzed the interaction of the sleep aid eszopiclone (ESZ) and antidepressant fluoxetine (FLX) on social defeat stress (SDS) in the mouse. Beta adrenoreceptors, brain-derived neurotrophic factor (BDNF) and cAMP response element binding protein (CREB) expression in the hippocampus and frontal cortex were also analyzed. Subjects were adult male ‘intruder’ C57/B6 mice that were exposed to a retired ‘resident’ male breeder ICR mouse in this animal's home cage for a 5min period for each of 10 consecutive days, and the resident established physical dominance. The following day, all animals were assigned to one of four drug treatment groups, and treatment was given for up to 18days: vehicle, ESZ only (3mg/kg), FLX (10mg/kg) only, or ESZ+FLX. A social interaction test was given on days 1, 5, 10, and 15 of drug treatment to assess SDS. Results showed that the ESZ+FLX group spent less time in avoidance zones during the interaction test at days 1 and 5, and more time in the interaction zone at day 5 compared to defeated mice given vehicle. All drug treatment groups spent more time in the interaction zone compared to defeated mice given vehicle on day 1 as well as day 10. SDS completely dissipated by the fourth interaction test according to both behavioral measures. Neurochemically, SDS did not produce changes in any marker analyzed. This study shows the combination of ESZ and FLX alleviated SDS, but a neurochemical correlate remains elusive. ► Eszopiclone (ESZ) and fluoxetine (FLX) cocktail reduced social defeat stress in mice. ► The treatment combination of ESZ and FLX was affective only at 1 and 5days after induction. ► These findings are similar to past clinical work in major depressive disorder. ► Differential findings were shown depending on the dependent measure used. ► Neurochemically, no drug treatment affected any marker assayed.