RESUMO
Abstract Tropaeolum majus L., Tropaeolaceae, popularly known in Brazil as 'capuchinha' is widely used due its anti-inflammatory, antiseptic, anti-hypertensive and anti-depressive properties. However, scientific investigations about its effects on the central nervous system are still scarce. This study investigated the central pharmacological actions of the prolonged treatment with a hydroethanolic extract of T. majus in male Wistar rats in the elevated plus maze and hole-board behavioral models. For this, rats were daily treated with distillated water (negative control); diazepam (1 mg/kg) or hydroethanolic extract of T. majus (75, 150 and 300 mg/kg), for 29 days (by gavage) and were submitted to elevated plus maze and hole-board. Animals treated with all hydroethanolic extract of T. majus or diazepam doses increased the percentage of entries in open arms when compared to control group. However, only treatment with diazepam increased the length of time spent in the open arms of the elevated plus maze. No differences between all groups were observed regardless rearing, grooming, stretched-attend postures and defecation rates. In the HB test, in opposite to diazepam, treatment with hydroethanolic extract of T. majus did not interfere in the exploratory activity of rats. The hydroethanolic extract of T. majus promotes anxiolytic-like effects when orally administered in rats.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Lavandula angustifolia (lavender) inhalation has been used in folk medicine for the treatment of anxiety, and clinical and animal studies have corroborated its anxiolytic effect, although its mechanism of action is still not fully understood. AIMS OF THE STUDY: The objective of the present study was to determine whether the GABAA/benzodiazepine complex or serotonin neurotransmission mediates the anxiolytic-like effect of lavender essential oil. MATERIALS AND METHODS: Male Swiss mice were subjected to the marble-burying test after being exposed to the aroma of lavender essential oil (1-5%), amyl acetate (5%; used as a behaviorally neutral odor), or distilled water for 15 min via inhalation. Additionally, the effect of 5% lavender essential oil was also evaluated in mice subjected to the elevated plus maze. GABAA/benzodiazepine mediation was evaluated by pretreating the mice with the GABAA receptor antagonist picrotoxin before the marble burying test and [(3)H]flunitrazepam binding to the benzodiazepine site on the GABAA receptor. Serotonergic mediation was studied by pretreating the mice with O-methyl-[3H]-N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY100635), a serotonin 5-HT1A receptor antagonist before the marble burying test. We also evaluated changes in the pharmacologically induced serotonin syndrome and the effects of combined administration of subeffective doses of lavender essential oil and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). RESULTS: Lavender essential oil (1-5%) decreased the number of marbles buried compared with the control and amyl acetate groups. In the elevated plus maze, 5% lavender essential oil inhalation increased the percentage of time spent on and number of entries into the open arms compared with controls. No effect was seen in the number of closed arm entries or number of beam interruptions in the automated activity chamber. Pretreatment with the GABAA receptor antagonist picrotoxin (0.5mg/kg) did not modify the behavioral effect of 5% lavender essential oil in the marble-burying test. Lavender essential oil also did not alter [(3)H]flunitrazepam binding to the benzodiazepine site on the GABAA receptor. Pretreatment with the serotonin 5-HT1A receptor antagonist WAY100635 (3mg/kg) blocked the anxiolytic-like effect of lavender essential oil and the 5-HT1A receptor agonist 8-OH-DPAT (3mg/kg). A combination of ineffective doses of 8-OH-DPAT (0.5mg/kg) and lavender essential oil (0.1%) reduced the number of marbles buried. Finally, 5% lavender essential oil attenuated the serotonin syndrome induced by 40 mg/kg fluoxetine plus 80 mg/kg 5-hydroxytryptophan. CONCLUSIONS: These results indicate an important role for the serotonergic system in the anxiolytic-like effect of lavender essential oil.
Assuntos
Ansiolíticos/administração & dosagem , Óleos Voláteis/administração & dosagem , Óleos de Plantas/administração & dosagem , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Administração por Inalação , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Diazepam/metabolismo , Flunitrazepam/metabolismo , Antagonistas de Receptores de GABA-A/farmacologia , Lavandula , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Picrotoxina/farmacologia , Piperazinas/farmacologia , Piridinas/farmacologia , Ratos , Receptores de GABA-A/metabolismo , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Síndrome da Serotonina , Transmissão SinápticaRESUMO
Protein kinase C (PKC) is an important cellular target for mood stabilizers such as lithium and valproate, and tamoxifen, an antiestrogenic drug with PKC inhibition activity, also demonstrates an antimanic effect. Thus, the aim of the present study was to evaluate whether the antimanic effect of tamoxifen is mediated through the PKC inhibitory and/or the antiestrogenic action(s) of the drug. In the present study, the effects of tamoxifen, chelerythrine (a PKC inhibitor) and medroxyprogesterone (an antiestrogenic drug) were investigated in amphetamine-induced hyperlocomotion of mice, an animal model of a manic state. Lithium carbonate (100 and 150 mg/kg, i.p.), tamoxifen (1.0 mg/kg, i.p.) and chelerythrine (1 microg/site, i.c.v.) completely blocked the amphetamine-induced hyperlocomotion. However, while the intermediate medroxyprogesterone dose (3.0 mg/kg, i.p.) partially reduced the amphetamine-induced hyperlocomotion, lower (1.0 mg/g) and higher (6.0 mg/kg) doses produced no effect. Our results indicate a major role for PKC inhibition in the antimanic-like effect of tamoxifen, although its antiestrogenic action may also contribute to this effect.