AB-Free Kava Suppresses Tobacco Smoke-Induced CREB Phosphorylation in the Mouse Cerebellum

Abstract

IntroductionOur recent studies revealed the potential of AB-free kava as a novel therapeutic candidate against tobacco use disorder while the underlying mechanism remains to be elucidated. The cerebellum region in the brain has recently been reported to be involved in tobacco smoke withdrawal. The cAMP response element-binding protein (CREB) activation via phosphorylation has also been reported to contribute to substance abuse, including tobacco use disorder. Our early pre-clinical work revealed the potential of AB-free kava to suppress tobacco smoke-induced CREB activation in lung tissues. MethodsIn this study, we investigated the impact of tobacco smoke exposure on the levels of phosphorylated CREB (p-CREB) in the mouse cerebellum and evaluated the effects of AB-free kava. ResultsFour different regimens of tobacco smoke exposure consistently increased the levels of p-CREB in the cerebellum. Importantly, AB-free kava effectively suppressed tobacco smoke-induced increase in p-CREB to levels comparable to mice without tobacco smoke exposure. ConclusionsCREB activation in the cerebellum is a potential mechanism involved in tobacco use disorder, and our data provide preliminary evidence for the protective potential of AB-free kava.