AB-free Kava reduces anxiety-like behavior without preventing nicotine-induced exploration suppression in mice

Introduction Tobacco use is the leading preventable cause of death worldwide. Anxiety increases the risk for smoking, and smoking in turn increases the risk for anxiety disorders. There is therefore a need to identify interventions that reduce anxiety, in general and in the context of smoking. Kava (Piper methysticum), a natural product with a long history of indigenous use, has been shown to have anxiolytic and calming effects and reduce nicotine withdrawal. The current study examined whether kava without the hepatotoxic flavokavains A and B (AB-free) could reduce anxiety-like behavior in mice repeatedly treated with nicotine. Methods Male and female C57BL/6N mice received either a control diet or an AB-free kava-supplemented diet and underwent two blocks of nicotine treatments. Mice underwent a first block of five every-other-day injections of nicotine (0.5 mg/kg) or saline, with open field testing after each injection, followed 1 week later by a nicotine challenge. A second block of injections was given using the same injection schedule, followed by a second challenge 1 week later, and 2 weeks afterward mice received a final challenge in a novel open field. Results During the first treatment block, nicotine significantly reduced locomotor activity and center time. There was a significant diet × treatment interaction on center time, with AB-free kava significantly increasing center time in saline-treated but not nicotine-treated mice. During the final challenge in a novel open field, nicotine again significantly reduced locomotor activity and center time, and AB-free kava significantly increased center time irrespective of nicotine treatment, without affecting locomotor activity. These effects remained significant when cage was included as a random factor. Discussion These results suggest that AB-free kava has anxiolytic-like effects without reducing locomotor activity but does not prevent nicotine-induced suppression of exploratory behavior.