Anxiolytic properties of Piper methysticum extract samples and fractions in the chick social-separation-stress procedure

Piper methysticum extract (Kava kava) possesses anxiolytic properties. However, it is unknown whether these effects are best predicted by total kavalactone content or by one or more of its primary kavalactone constituents. Using the chick social separation-stress procedure as an anxiolytic bioassay, P. methysticum samples containing 12.8-100.0% total kavalactones (Exp. 1) and fractions containing 1-6 kavalactones of varying concentrations (0.1-67.5%; Exps. 2-3) were screened for activity and compared against a 5.0 mg/kg dose of chlordiazepoxide (CDP; Exp. 3). Eight-day-old chicks received IP injections of either vehicle or test compounds 30 min before being placed in the presence of two conspecifics or in isolation for a 3 min observation period. Dependent measures were ventral recumbency latency (sedation), distress vocalizations, and a measure of stress-induced analgesia (in Exps. 1 and 2 only). P. methysticum extract samples attenuated distress vocalizations in a concentration-dependent manner. The P. methysticum fraction that contained the highest concentration of dihydrokavain attenuated distress vocalizations in a manner equivalent to that of CDP. The extract samples and fractions that possessed anxiolytic properties did not possess the sedative properties found in CDP. Collectively, these findings suggest that dihydrokavain may be necessary and sufficient in mediating the anxiolytic properties of P. methysticum extract.