Campos Glenda Viggiano, de Noronha Sylvana Rendeiro, de Souza Aline Arlindo, Lima Paulo Marcelo, Abreu Aline Rezende, Chianca-Jr Deoclecio, de Menezes Rodrigo Cunha
Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto, MG, Brazil; Graduate Program in Biological Sciences CBIOL/NUPEB, Federal University of Ouro Preto, Ouro Preto, Brazil.
Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto, MG, Brazil; Graduate Program in Biological Sciences CBIOL/NUPEB, Federal University of Ouro Preto, Ouro Preto, Brazil.
Behav Brain Res. 2019 Jan 14;357-358:57-64. doi: 10.1016/j.bbr.2018.03.029. Epub 2018 Mar 19.
Severe food restriction (FR), as observed in disorders like anorexia nervosa, has been associated to the reduction of estrogen levels, which in turn could lead to anxiety development. Estrogen receptors, mainly ERβ type, are commonly found in the dorsal raphe nucleus (DRN) neurons, an important nucleus related to anxiety modulation and the primary source of serotonin (5-HT) in the brain. Taking together, these findings suggest an involvement of estrogen in anxiety modulation during food restriction, possibly mediated by ERβ activation in serotonergic DRN neurons. Thus, the present study investigated the relationship between food restriction and anxiety-like behavior, and the involvement of DRN and ERβ on the modulation of anxiety-like behaviors in animals subjected to FR. For that, female Fischer rats were grouped in control group, with free access to food, or a FR group, which received 40% of control intake during 14 days. Animals were randomly treated with 17β-estradiol (E2), DPN (ERβ selective agonist), or their respective vehicles, PBS and DMSO. Behavioral tests were performed on Elevated T-Maze (ETM) and Open Field (OF). Our results suggest that FR probably reduced the estrogen levels, since the remained in the non-ovulatory cycle phases, and their uterine weight was lower when compared to control group. The FR rats showed increased inhibitory avoidance latency in theETM indicating that FR is associated with the development of an anxiety-like state. The injections of both E2 and DPN into DRN of FR animals had an anxiolytic effect. Those data suggest thatanxiety-like behavior induced by FR could be mediated by a reduction of ERβ activation in the DRN neurons, probably due to decreased estrogen levels.
在神经性厌食症等疾病中观察到的严重食物限制（FR）与雌激素水平降低有关，而这反过来可能导致焦虑的产生。雌激素受体，主要是ERβ类型，常见于中缝背核（DRN）神经元中，中缝背核是一个与焦虑调节相关的重要核团，也是大脑中血清素（5-HT）的主要来源。综合这些发现表明，雌激素在食物限制期间参与焦虑调节，可能是通过血清素能DRN神经元中的ERβ激活介导的。因此，本研究调查了食物限制与焦虑样行为之间的关系，以及DRN和ERβ在食物限制动物焦虑样行为调节中的作用。为此，将雌性Fischer大鼠分为对照组，可自由获取食物，或FR组，在14天内给予对照组摄入量的40%。动物被随机用17β-雌二醇（E2）、DPN（ERβ选择性激动剂）或它们各自的载体PBS和二甲基亚砜进行处理。在高架T迷宫（ETM）和旷场（OF）上进行行为测试。我们的结果表明，FR可能降低了雌激素水平，因为它们处于非排卵周期阶段，并且与对照组相比，其子宫重量较低。FR大鼠在ETM中表现出抑制性回避潜伏期增加，表明FR与焦虑样状态的发展有关。向FR动物的DRN注射E2和DPN均具有抗焦虑作用。这些数据表明，FR诱导的焦虑样行为可能是由DRN神经元中ERβ激活减少介导的，这可能是由于雌激素水平降低所致。
