Attenuation of Anxiety Behaviours by Xylopic Acid in Mice and Zebrafish Models of Anxiety Disorder

Anxiety disorders affect people worldwide with disabling symptoms. Xylopic acid, an ent-kaurane diterpene, exerts central nervous system depressant, opioid receptor-mediated analgesic and anti-neuropathic pain effects. Agents acting as CNS depressants can ameliorate anxiety disorders hence, this study evaluates the anxiolytic potential of xylopic acid in mice and zebrafish. Xylopic acid was given orally at 3, 10 or 30 mg kg-1 to mice or 3, 10 or 30 µM to zebrafish.  Anxiety was assessed in mice using open field (OFT), novelty-induced hypophagia (NIH), and elevated plus maze (EPM) models and in zebrafish using novel tank (NT) and scototaxis (ST) models. Additionally, xylopic acid’s activity on anxiety induced by alcohol withdrawal was also evaluated. Xylopic acid at doses 3-30 mg kg-1 reduced latency to feeding in mice in the hyponeophagia test for anxiety and also significantly reduced thigmotaxis in the OFT at 30 mg kg-1 (P<0.001). All mice given xylopic acid significantly spent more time in the open arms of the EPM (P<0.001). At 10 µM xylopic acid-treated zebrafish exhibited significant (P<0.001) reduction in time spent at bottom of novel tank but it did not reduce scototaxis in the light-dark test. Furthermore, xylopic acid attenuated increased bottom dwelling induced by alcohol withdrawal in zebrafish. The doses of xylopic acid used did not impair locomotion in the chimney test for mice. These findings indicate anxiolytic-like properties of xylopic acid in mice and zebrafish models of anxiety disorder.