Abstract:
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
