OBJECTIVE: Remarkably high rates of abstinence occur among alcohol-dependent persons after a liver transplant. This was thought to be solely due to selection or other nonbiological factors. Observing sustained abstinence for many months to years after a liver transplant, however, we asked whether immunosuppressants might exert a biological effect that supported abstinence from ethanol. METHOD: We hypothesized that cyclosporine-A-treated mice would drink less ethanol given a choice between water and 10% ethyl alcohol. After a 3-day ethanol conditioning period, C57bl/6j mice (n = 20) medicated with cyclosporine-A (50 mg/kg) and a control group of unmedicated mice (n = 20) injected with saline were given free access to either water or the ethanol solution. RESULTS: The medicated mice drank significantly less ethanol throughout the 11-day choice protocol. This was significant whether measured by mean alcohol consumption per day (p = .003) or by alcohol preference as a percent of total liquid intake per day (p = .03). The two groups did not differ significantly in total daily fluid consumption. CONCLUSION: These data suggest that cyclosporine-A lowers alcohol preference in mice. Mechanism of action, similar effects by other centrally acting immunosuppressants and translation to humans all remain to be studied. If fruitful, elucidating the actions of cyclosporine and other immunosuppressants that activate central nervous system receptors may illuminate the pathophysiology of alcohol use and addiction.
OBJECTIVE: Remarkably high rates of abstinence occur among alcohol-dependent persons after a liver transplant. This was thought to be solely due to selection or other nonbiological factors. Observing sustained abstinence for many months to years after a liver transplant, however, we asked whether immunosuppressants might exert a biological effect that supported abstinence from ethanol. METHOD: We hypothesized that cyclosporine-A-treated mice would drink less ethanol given a choice between water and 10% ethyl alcohol. After a 3-day ethanol conditioning period, C57bl/6j mice (n = 20) medicated with cyclosporine-A (50 mg/kg) and a control group of unmedicated mice (n = 20) injected with saline were given free access to either water or the ethanol solution. RESULTS: The medicated mice drank significantly less ethanol throughout the 11-day choice protocol. This was significant whether measured by mean alcohol consumption per day (p = .003) or by alcohol preference as a percent of total liquid intake per day (p = .03). The two groups did not differ significantly in total daily fluid consumption. CONCLUSION: These data suggest that cyclosporine-A lowers alcohol preference in mice. Mechanism of action, similar effects by other centrally acting immunosuppressants and translation to humans all remain to be studied. If fruitful, elucidating the actions of cyclosporine and other immunosuppressants that activate central nervous system receptors may illuminate the pathophysiology of alcohol use and addiction.
Authors: Kolter B Grigsby; Antonia M Savarese; Pamela Metten; Barbara J Mason; Yuri A Blednov; John C Crabbe; Angela R Ozburn Journal: Neurosci Insights Date: 2020-11-25