AB-free kava suppresses tobacco smoke-induced CREB phosphorylation in the mouse cerebellum

• Tobacco smoke exposure consistently increased cAMP response element-binding protein (CREB) phosphorylation in mice cerebellum under different exposure regimens. • AB-free kava effectively suppressed tobacco smoke-induced p-CREB elevation in mice cerebellum. • The impact of AB-free kava suppression of tobacco smoke-induced p-CREB elevation remains to be determined. Our 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 been reported to be involved in tobacco 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. In 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. Four different regimens of tobacco smoke exposure consistently increased the levels of p-CREB in the cerebellum. AB-free kava effectively suppressed tobacco smoke-induced increase in p-CREB to levels comparable to mice without tobacco smoke exposure. Our data provide preliminary evidence that CREB activation in the cerebellum is a potential mechanism involved in tobacco use disorder and the protective potential of AB-free kava.