Combined Effects of Acamprosate and Escitalopram on Ethanol Consumption in Mice

Background Major depression is one of the most prevalent psychiatry comorbidities of alcohol use disorders (AUD). As negative emotions can trigger craving and increase the risk of relapse, treatments that target both conditions simultaneously may augment treatment success. Previous studies showed a potential synergistic effect of Food and Drug Administration approved medication for AUD acamprosate and the antidepressant escitalopram. In this study, we investigated the effects of combining acamprosate and escitalopram on ethanol (EtOH) consumption in stress‐induced depressed mice. Methods Forty singly housed C57BL/6J male mice were subjected to chronic unpredictable stress. In parallel, 40 group‐housed male mice were subjected to normal husbandry. After 3 weeks, depressive‐ and anxiety‐like behaviors and EtOH consumption were assessed. For the next 7 days, mice were injected with saline, acamprosate (200 mg/kg; twice/d), escitalopram (5 mg/kg; twice/d), or their combination (n = 9 to 11/drug group/stress group). Two‐bottle choice limited‐access drinking of 15% EtOH and tap water was performed 3 hours into dark phase immediately after the daily dark phase injection. EtOH drinking was monitored for another 7 days without drug administration. Results Mice subjected to the chronic unpredictable stress paradigm for 3 weeks showed apparent depression‐ and anxiety‐like behaviors compared to their nonstressed counterparts including longer immobility time in the forced swim test and lower sucrose preference. Stressed mice also displayed higher EtOH consumption and preference in a 2‐bottle choice drinking test. During the drug administration period, the escitalopram‐only and combined drug groups showed significant reduction in EtOH consumption in nonstressed mice, while only the combined drug group showed significantly reduced consumption in stressed mice. However, such reduction did not persist into the postdrug administration period. Conclusions The combination of acamprosate and escitalopram suppressed EtOH intake in both nonstressed and stressed mice; hence, this combination is potentially helpful for AUD individuals with or without comorbid depression to reduce alcohol use. Comorbidity between alcohol use disorder and depression is common and poses treatment challenge. Here, we investigated the effects of combining acamprosate and escitalopram on ethanol drinking in mice displaying depression‐like behaviors after chronic unpredictable stress. We observed that co