Anxiolytic effects of kava extract and kavalactones in the chick social separation-stress paradigm

Rationale: Piper methysticum extract (kava kava) possesses numerous therapeutic properties, but it is unknown which of its principle constituents (kavalactones) subserve such effects. Objectives: This experiment sought to characterize the putative anxiolytic properties of P. methysticum extract and its six principle kavalactones in the chick social separation-stress paradigm. Methods: Eight-day-old chicks received intraperitoneal injections of either vehicle, chlordiazepoxide (5.0 mg/ml per kg). P. methysticum extract (containing 30% kavalactones), kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, or desmethoxyyangonin (30 mg/ml per kg for kava compounds) 30 min prior to being tested in the presence of two conspecifics or in isolation for a 3-min observation period. Latency to adopt a ventral recumbent posture to index sedation, number of vocalizations to index separation distress, and a composite pain score (in response to 50 mul 0.10% formalin injection into the plantar surface of the foot) to index stress-induced analgesia served as dependent measures. Results: Both chlordiazepoxide and P. methysticum extract attenuated separation-induced distress vocalizations and stress-induced analgesia. Dihydrokavain attenuated separation-induced distress vocalizations. Conclusions: These findings suggest that the anxiolytic effects of P. methysticum extract may be mediated, in part, by dihydrokavain.