de Azevedo Camin Nathália, Traslaviña Guillermo Andrey Ariza, de Barcellos Filho Procópio Cleber Gama, Franci Celso Rodrigues
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Brain Res. 2022 May 1;1782:147833. doi: 10.1016/j.brainres.2022.147833. Epub 2022 Feb 18.
Several brain structures responsible for controlling stress responses reach maturity during adolescence. Therefore, acute or chronic stress in prepuberty may negatively affect stress responses as well as behavior in adulthood. The hypothalamus-pituitary-adrenal axis (HPA) is part of the stress system whose inhibitory control is regulated by glucocorticoids through mineralocorticoid (MR) and glucocorticoid (GR) receptors. In this study, we aimed to determine whether MR or GR blockade after stress in adolescence prevents changes in exploratory behavior and HPA axis control in adult female rats. Adolescent female rats (26 days old) were submitted to one or seven daily restraint sessions followed by administration of MR (spironolactone) or GR (RU-486) antagonists. At 60 days old, animals were evaluated in the elevated plus maze and at 61 days old rats were subjected to acute stress to evaluate the HPA response. The chronic restraint in the adolescence induced an anxiogenic effect in the adult animals that was reverted by either MR or GR antagonist. In the same way chronic stress reduced the HPA axis activity by blunted corticosterone (CORT) secretion and decreased the activation of Corticotropin Releasing Hormone (CRH) neurons in the paraventricular nucleus. The post-stress blocking of GR independently restored the CORT secretion without effect on central activation. The acute stress in the adolescence had minor enduring effects. We concluded that the use of RU-486 and spironolactone after stress in the early adolescence can improve behavioral changes induced by stress whereas RU-486 only showed effect on the HPA axis response in adulthood.
负责控制应激反应的几个脑结构在青春期达到成熟。因此，青春期前的急性或慢性应激可能会对成年后的应激反应以及行为产生负面影响。下丘脑 - 垂体 - 肾上腺轴（HPA轴）是应激系统的一部分，其抑制性控制由糖皮质激素通过盐皮质激素（MR）和糖皮质激素（GR）受体进行调节。在本研究中，我们旨在确定青春期应激后阻断MR或GR是否能预防成年雌性大鼠探索行为的改变以及HPA轴控制的变化。将青春期雌性大鼠（26日龄）每天进行一次或七次束缚，随后给予MR拮抗剂（螺内酯）或GR拮抗剂（RU - 486）。在60日龄时，在高架十字迷宫中对动物进行评估，在61日龄时对大鼠施加急性应激以评估HPA反应。青春期的慢性束缚在成年动物中诱导出焦虑样效应，而MR或GR拮抗剂均可使其恢复。同样，慢性应激通过减弱皮质酮（CORT）分泌降低了HPA轴活性，并减少了室旁核中促肾上腺皮质激素释放激素（CRH）神经元的激活。应激后阻断GR可独立恢复CORT分泌，而对中枢激活无影响。青春期的急性应激产生的持久影响较小。我们得出结论，青春期早期应激后使用RU - 486和螺内酯可以改善应激诱导的行为变化，而RU - 486仅对成年期的HPA轴反应有影响。
