Kielmeyera coriacea Mart. (Clusiaceae), known as "Pau Santo", is used to treat several tropical diseases. The hydroethanolic extract (HE) of Kielmeyera coriacea stems and its semi-pure dichloromethane constituent (DCM) produced an anti-immobility effect in rats submitted to the forced swimming test (FST), suggesting a antidepressant-like profile. This study evaluated the effect of intra-median raphe nucleus (MRN) microinjection of 1,3,7-trihydroxy-2-(3-methylbut-2-enyl)-xanthone, present in large quantity in the HE from Kielmeyera coriacea stems, on immobility behaviour in the FST in rats. The effects of xanthone were compared with intra-MRN microinjections of Way100635 (5-HT1A antagonist) or (+) 8-OH-DPAT (5-HT1A agonist). Locomotor activity in the open-field test (OFT) was evaluated as a complementary measure. Xanthone (0.3ng) or Way100635 (2.5microg) reduced, whereas (+) 8-OH-DPAT (5.0microg) increased immobility time in the FST. Way100635 (2.5 or 5.0microg) completely reversed the effects of (+) 8-OHDPAT (5.0microg), and potentiated the anti-immobility effect of the ineffective dose of xanthone (0.2ng) in the FST. The association of effective doses of (+) 8-OH-DPAT (5.0microg) and xanthone (0.3ng) annulled the effect of each compound on immobility time. These results suggest that xanthone acts as an antagonist at 5-HT1A autoreceptors in MRN and increases serotonin (5-HT) availability in projection regions, proving to be a prototype drug that may be useful in mood isorders such as depression, or indeed be a beneficial adjunctive treatment improving the efficacy and/or accelerating the effects of antidepressant drugs in patients with major depression.

No abstract

No abstract