RESUMO
The lateral septum (LS) is a limbic brain region that receives serotonergic projections from raphe neurons and participates in the modulation of stress responses and affective states. The present study determined whether mineralocorticoid receptors (MRs) and/or glucocorticoid receptors (GRs) located in the LS interact with the serotonergic system in the regulation of depressive-like behavior of rats subjected to the forced swimming test (FST). We also studied the effect of corticosterone release induced by the FST on MR- and GR-mRNA expression in the LS. Specifically, we studied the antidepressant-like effects of spironolactone (a MR antagonist), mifepristone (a GR antagonist), and the antidepressant clomipramine (CMI) administered directly into the LS. In addition, spironolactone and CMI actions were studied in animals with serotonergic depletion induced by dl-p-chlorophenylalanine (pCPA). Finally, adrenalectomized and Sham-operated rats were subjected to the FST to determine MR- and GR-mRNA expression in the LS at different post-FST intervals. The results showed that intraseptal injection of spironolactone, but not mifepristone induced antidepressant-like actions in the FST; this effect was blocked by pCPA treatment. CMI and spironolactone increased 5-HT concentrations in the LS of rats subjected to the FST. Increases in corticosterone release, induced by the FST, correlated with a decrease in MR-mRNA expression in the LS; no correlation was found with GR-mRNA expression. In conclusion, MRs in the lateral septum, but not GRs, participate in the regulation of depressive-like behavior of animals subjected to the FST. Both serotonin and corticosterone play an important role in MR actions in the LS.
Assuntos
Clomipramina/farmacologia , Mifepristona/farmacologia , Antagonistas de Receptores de Mineralocorticoides , Receptores de Glucocorticoides/antagonistas & inibidores , Septo do Cérebro/efeitos dos fármacos , Serotonina/metabolismo , Espironolactona/farmacologia , Animais , Antidepressivos/farmacologia , Clomipramina/administração & dosagem , Corticosterona/metabolismo , Interações Medicamentosas , Fenclonina/farmacologia , Ácido Hidroxi-Indolacético/metabolismo , Resposta de Imobilidade Tônica/efeitos dos fármacos , Masculino , Microinjeções , Mifepristona/administração & dosagem , Mifepristona/antagonistas & inibidores , Ratos , Ratos Wistar , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/metabolismo , Septo do Cérebro/metabolismo , Espironolactona/administração & dosagem , Espironolactona/antagonistas & inibidoresRESUMO
O efeito do veneno de abelha foi avaliado na artrite induzida por antígeno, em coelhos. O veneno de abelha foi ministrado 7 dias antes da indução da artrite, por via subcutânea, nas doses de 1,5; 3,0 e 6,0 mg/Kg/dia. O líquido sinovial foi coletado, para avaliação do número total e diferencial de células; permeabilidade vascular; determinação de prostaglandina E2 e metabólitos de óxido nítrico. A influência de glicocorticóides endógenos foi investigada com metopirona e RU 38 486, em animais que receberam veneno de abelha (1,5 mg/Kg/dia). O pré-tratamento com veneno de abelha (1,5 mg/Kg/dia) reduziu o influxo de leucócitos para a articulação inflamada, assim como os níveis de prostaglandina E2. Esse efeito não foi observado nos animais que receberam metopirona. O RU 38 486 não alterou a atividade antiinflamatória do veneno de abelha.The effect of bee venom was evaluated on antigen induced arthritis, in rabbits. Bee venom was administrated subcutaneously, 7 days before arthritis was induced, in different doses: 1,5; 3,0 and 6,0 g/Kg/day. Total and differential leucocyte migration, protein leakage, intraarticular concentration of prostaglandina E2 and nitric oxide metabolites were quantified in sinovial fluid. The influence of endogenous glucocorticoids was investigated with metyrapone and RU 38 486, in animals treated with bee venom (1,5g/Kg/day). Pre-treatment with bee venom (1,5g/Kg/day) were effective in reducing leucocyte afflux, compared with control animals. Prostaglandin E2 levels were also significantly reduced in this group. This effect was not observed in animals treated with metyrapone. The anti-inflammatory activity of bee venom was not affected by RU 38 486...