title: Effect of xanthone from Kielmeyera coriacea stems on serotonergic neurons of the median raphe nucleus.
abstract: 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.
authors.affiliation: Department of Pharmacy and Pharmacology, State University of Maringá; Av Colombo 5790, 87020-900 Maringá, Paraná, Brazil.
authors.forename: V R
authors.initials: VR
authors.lastname: Sela
authors.forename: I
authors.initials: I
authors.lastname: Hattanda
authors.forename: C M
authors.initials: CM
authors.lastname: Albrecht
authors.forename: C B
authors.initials: CB
authors.lastname: De Almeida
authors.forename: S
authors.initials: S
authors.lastname: Obici
authors.forename: D A
authors.initials: DA
authors.lastname: Cortez
authors.forename: E A
authors.initials: EA
authors.lastname: Audi
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D028084:Clusiaceae / Q000737:chemistry*; D046353:Immobility Response, Tonic / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018547:Plant Stems; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000302:isolation & purification / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D044004:Xanthones / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D010936:Plant Extracts; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044004:Xanthones; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C009689:xanthone