RESUMEN
The current research studied the behavior adopted in the elevated plus maze (EPM) of rats previously subjected to a social defeat using the resident-intruder paradigm. One day after defeat, intruder animals exhibited an anxiogenic-like behavior in the EPM. In addition, we also evaluated the role of the corticosteroid receptor system (minerlocorticoid - MR - and glucocorticoid - GR - receptors) from the lateral septum (LS) on the anxiety generated by social defeat. The LS is an area of the aversive circuitry that is preferentially activated in passive defensive postures, and participates - together with other brain areas - in the modulation of aversive states. Intruder animals were infused into the LS with the MR or GR antagonist (ZK 91587 and RU 38486, respectively) and then submitted to social stress. All rats were tested in the EPM 1 day later. Only the administration of the GR antagonist, but not the MR antagonist, into the LS normalized the anxiogenic response induced by defeat. Furthermore, we examined whether a single injection of corticosterone (CS) could induce the same influence on the behavior in the EPM as that observed after social defeat. Moreover, we explored the effect of local infusions of MR or GR antagonists into the LS on the behavior exhibited by CS-treated rats in a subsequent EPM exposure. CS administration also exerted an increased anxiogenic-like behavior, which was normalized only by the local infusion of the GR antagonist. Based on these findings, we suggest that CS secreted by emotionally relevant stimuli acting via GR in LS plays an important role in the modulation of the emotional sequelae induced by social defeat.
Asunto(s)
Ansiedad/metabolismo , Corticosterona/fisiología , Dominación-Subordinación , Receptores de Glucocorticoides/metabolismo , Núcleos Septales/metabolismo , Análisis de Varianza , Animales , Reacción de Prevención/fisiología , Emociones/fisiología , Conducta Exploratoria/fisiología , Femenino , Masculino , Ratas , Ratas Wistar , Receptores de Mineralocorticoides/metabolismo , Medio SocialRESUMEN
Corticosterone (CS) has been shown to regulate behavior in the learned helplessness (LH) paradigm. Here we provide evidence for a U-shaped relationship between the increasing doses of CS administered and escape failures in the LH model. Replacement with CS (20-400 microg/ml in drinking water) in adrenalectomized (ADX) animals was utilized to examine how the selective activation of mineralocorticoid (MR) and glucocorticoid (GR) receptors is related to the behavioral impairments induced by inescapable shock (IS). Available MR and GR levels were determined in hippocampal cytosol by radioligand binding assays. Non-CS replaced ADX animals showed a high percentage of escape failures assessed 48 h after IS. A CS does of 100 microg/ml given to ADX animals markedly reduced escape failures and resulted in an almost total reduction of available MR associated with a partial reduction of GR. However, the administration of aldosterone (ALDO), a selective MR agonist, was not sufficient to restore normal coping behavior. Moreover, an important role for GR was further shown by means of the specific GR antagonist, RU 38486, which blocked the reduction of LH in ADX rats that were given 100 microg/ml CS. Higher doses of CS given to ADX rats reinstated the LH behavior, and SHAM rats that produced stress CS levels also produced LH behavior. The results indicate a U-shaped dose response function with both negligible and high CS levels being associated with LH behavior. Hence, along with a moderate reduction of available GR level in the cytosol, a large decrease in MR availability seems to be necessary to prevent the acquisition and expression of LH. However, very high reduction of available GR is associated with LH behavior.
Asunto(s)
Glándulas Suprarrenales/fisiología , Conducta Animal/efectos de los fármacos , Desamparo Adquirido , Esteroides/farmacología , Aldosterona/farmacología , Animales , Reacción de Prevención/efectos de los fármacos , Corticosterona/metabolismo , Corticosterona/farmacología , Citosol/efectos de los fármacos , Citosol/metabolismo , Relación Dosis-Respuesta a Droga , Electrochoque , Antagonistas de Hormonas/farmacología , Bombas de Infusión Implantables , Masculino , Mifepristona/farmacología , Antagonistas de Receptores de Mineralocorticoides , Actividad Motora/efectos de los fármacos , Ratas , Ratas Wistar , Receptores de Glucocorticoides/antagonistas & inhibidores , Estrés Psicológico/psicologíaRESUMEN
OBJECTIVES: Experimental autoimmune encephalomyelitis (EAE) was induced to investigate the levels of circulating total testosterone (TT) and the possible association of corticosterone with the steroid-producing capacity of the testes. SETTING AND DESIGN: We determined gonad weights, serum TT and corticosterone levels during the development of EAE in male rats. METHODS: Active EAE was induced in young male Wistar rats by injection of whole myelin in complete Freund's adjuvant. All the rats were weighted and monitored daily for clinical signs and blooded during different phases of the disease. Serum TT was measured by radioimmunoassay and circulating corticosterone was determined using a competitive enzyme immunoassay. Also testes and seminal vesicles were removed to determine their weights. RESULTS: Seminal vesicle weights and serum TT levels diminished during the acute stage of the disease in all EAE rats and then they began gradually to increase, reaching the normal values at the post-recovery phase. Concomitantly a significant increase in serum corticosterone levels was observed during the acute EAE and the post-recovery phase was accompanied by a decline in corticosterone levels. MAIN FINDING: Our results indicated an inverse correlation between serum TT and corticosterone levels during the acute EAE. Moreover, the diminution of TT was not a consequence of an alteration of the testes induced by anti-myelin antibodies neither contributed by apoptosis of testis cells by exposure to corticosterone. CONCLUSIONS: The negative correlation between corticosterone and TT levels associated to EAE may be relevant in understanding the association of the endocrine system and the development of autoimmune demyelinating diseases.