IntroductionOvarian follicle failure and subsequent estradiol deficiency as a result of menopause leads to impairments in the cardiovascular system and brain. Reduction of estradiol levels is associated with the development of hypertension and anxiety, suggesting estradiol exerts cardioprotective and neuroprotective effects. Furthermore, studies have shown that estradiol deficiency increases circulating and tissues levels of the vasoconstrictor angiotensin II, which itself can increase anxiety responses. The paraventricular nucleus (PVN) is a brain area that has a high density of angiotensin type 1 receptors (AT1R) and beta‐estrogen receptors (ERβ). These observations suggest estradiol modulates anxiety responses in part through regulation of the renin angiotensin system (RAS). The aim of this study was to evaluate the impact of estradiol on anxiety‐like behavior and the neuronal activation on the PVN.MethodsThree month old (mo) female Fischer rats were divided into Intact (INT), ovariectomized (OVX) and Sham‐operated (SHAM) animal groups. Three weeks after surgery, the animals were submitted to a battery of anxiety tests including the elevated T‐maze (ETM), open field (OF) and light/dark box (LDB). Ninety minutes later, the animals were euthanized and the brains were collected to assess c‐Fos activity. Anxiety tests in INT animals were conducted during proestrus or diestrus phase while Sham animals were tested in the diestrus phase. A handling group (H), which was not exposed to behavioral tests, was added as a control for the c‐Fos protocol.ResultsOur results found that the different phases of the estrus cycle did not influence the behavior of the INT group on the ETM, OF and LDB behavioral tests (p>0.05, Mann‐Whitney test). In contrast, the OVX group showed increased inhibitory avoidance and reduced escape latencies in the ETM (p<0,05, Mann‐Whitney test) and also reduced numbers of entries on the dark side of the LDB test (p<0.05, Mann‐Whitney test) in comparison to the Sham control, indicating anxiety‐like behavior. Moreover, the OVX group showed higher neuronal activation in the PVN compared to the other animal groups including OVX‐H (p < 0.001), INT (p < 0.001), and Sham (p < 0.01) by one‐way ANOVA.ConclusionEstradiol deprivation caused by ovariectomy induces anxiety‐like behavior in a myriad of behavioral tests under conditions in which neuronal activation of the PVN occurs.Support or Funding InformationCAPES, CNPq, FAPEMIG, UFOPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.