This study was designed to analyze whether the sleep aid eszopiclone may facilitate the efficacy of fluoxetine on social defeat stress (SDS) in the mouse. Subjects were adult male ‘intruder’ C57/B6 mice that that were exposed to a retired ‘resident’ male breeder ICR mouse in this animal’s home cage for a 5 min period for 10 consecutive days. During this interaction, the resident would establish physical dominance of the intruder. After confrontation, the intruder was housed in a cage that allowed sensory contact with the resident mouse but that would not allow physical interaction during the 10-day period. Once the 10 days of interaction were complete, all animals were assigned to one of four drug treatment groups, and treatment was given for up to 18 days: saline treatment, fluoxetine (10 mg/kg) only, eszopiclone only (3 mg/kg), or fluoxetine + eszopiclone. A social interaction test was given on days 1, 5, 10, and 15 of drug treatment. Sucrose preference was also tested during the interaction test. Results showed that eszopiclone facilitated the action of fluoxetine on the interaction test at days 1 and 5, and these two groups were equivalent on days 10 and 15. SDS produced a significant decrease in sucrose preference that was not affected by drug treatment. This study demonstrates that eszopiclone facilitates the action of fluoxetine in the SDS paradigm, paralleling clinical studies that showed facilatory effects of the drug combination in depressed patients. Future work will examine neurochemical mechanisms underlying the effects of this drug combination

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 5 min 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 18 days: 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.