Previously, we have used various inhibitors of the proinflammatory NLRP3 inflammasome to show that reduction in inflammation via small molecule inhibitors may affect alcohol consumption and preference. Using therapeutic treatments to inhibit NLRP3, caspase-1, and IL-1β, we found a reduction in ethanol consumption and preference in a two-bottle choice test [18]. Thus, in the treatment of alcohol-related pathology such as alcoholic liver disease, some therapeutics may operate via a mechanism that includes reduced alcohol consumption. Using the two-bottle choice paradigm, we found that CVC treatment did not influence ethanol consumption or preference. Additionally, using the Lieber-DeCarli chronic alcohol consumption model, we observed no difference in alcohol consumption between control and CVC-treated mice. Therefore, we can conclude that the data presented here, which included a reduction of both peripheral macrophage infiltration to the CNS and markers of inflammation within the CNS parenchyma, is likely due to the direct effects of CVC blockade on the CCR2/5 receptors and is not related to a change in the amount of alcohol consumed and/or a preference for alcohol. This is consistent with our previous findings that CVC both prevented and ameliorated alcoholic liver disease in mice [55].
