The antidepressant-like effect of Hedyosmum brasiliense and its sesquiterpene lactone, podoandin in mice: Evidence for the involvement of adrenergic, dopaminergic and serotonergic systems

We have recently shown that the ethanol extract of the leaves of Hedyosmum brasiliense exhibits an antidepressant-like effect in the tail suspension and forced swimming tests in mice. The present study investigates the mechanisms involved in the antidepressant-like effect of H. brasiliense extract, together with the antidepressant potential of podoandin, an isolated sesquiterpenoid. H. brasiliense (50 mg/kg, i.p.) and podoandin (10 mg/kg, i.p.) decreased the immobility time in the forced swimming test, without any accompanying changes in ambulation in the open-field test. The anti-immobility effect of the H. brasiliense extract was prevented by pre-treating the mice with ondansetron, NAN 190, pindolol, prazosin, yohimbine, haloperidol, SCH23390, and sulpiride. On the other hand, pre-treating the mice with: p-chlorophenylalanine (4 consecutive days), ketanserin, naloxone, naltrindole, bicuculline, phaclofen, or L-arginine did not block the antidepressant-like effect of H. brasiliense. In addition, pretreatment of the animals with methylene blue, NG-nitro-L-arginine or 7-nitroindazole, at subeffective doses, did not cause a synergistic effect with H. brasiliense extract at an effective dose in the forced swimming test. The anti-immobility effect of podoandin was also prevented by pre-treating the mice with NAN-190, ondansetron, prazosin, yohimbine, sulpiride and haloperidol. The results indicate that the antidepressant-like effect of H. brasiliense (and podoandin) is dependent on the serotonergic, noradrenergic and dopaminergic systems, but not on the GABAergic, opioid and oxidonitrergic systems. (C) 2011 Elsevier B.V. All rights reserved.