The Role of Estrogen in Anxiety-Like Behavior and Memory of Middle-Aged Female Rats

Abstract

Aging in women is associated with low estrogen, but also with cognitive decline and affective disorders. Whether low estrogen is causally responsible for these behavioral symptoms is not clear. Thus, we aimed to examine the role of estradiol in anxiety-like behavior and memory in rats at middle age. Twelve-month old female rats underwent ovariectomy (OVX) or were treated with 1 mg/kg of letrozole-an aromatase inhibitor. In half of the OVX females, 10 µg/kg of 17β-estradiol was supplemented daily for 4 weeks. Vehicle-treated sham-operated and OVX females served as controls. For behavioral assessment open field, elevated plus maze and novel object recognition tests were performed. Interaction between ovarian condition and additional treatment had the main effect on anxiety-like behavior of rats in the open field test. In comparison to control females, OVX females entered less frequently into the center zone of the open field (p < 0.01) and showed lower novel object discrimination (p = 0.05). However, estradiol-supplemented OVX rats had higher number of center-zone entries (p < 0.01), spent more time in the center zone (p < 0.05), and showed lower thigmotaxis (p < 0.01) when compared to OVX group. None of the hormonal manipulations affected anxiety-like behavior in the elevated plus maze test significantly, but a mild effect of interaction between ovarian condition and treatment was shown (p = 0.05). In conclusion, ovariectomy had slight negative effect on open-field ambulation and short-term recognition memory in middle-aged rats. In addition, a test-specific anxiolytic effect of estradiol supplementation was found. In contrast, letrozole treatment neither affected anxiety-like behavior nor memory.

Behaviors Related to Psychiatric Disorders and Pain Perception in C57BL/6J Mice During Different Phases of Estrous Cycle

“…However, the majority of preclinical and clinical studies have been carried out in male individuals, initially due to the perception that data acquired in females under different stages of the estrous cycle would be more varied than that obtained from males. Estrogen, a hormone that fluctuates over estrous cycle, and the agonist of its receptors has also been implicated in modulating animal behaviors in a large number of studies (Crider et al, 2018;Popov et al, 2020;Qu et al, 2020;Renczés et al, 2020;Ghazvini et al, 2021;Valdés-Sustaita et al, 2021). Consistently, preclinical studies discovered a statistical difference in psychiatry-and painrelated behavioral and physiological traits (Meziane et al, 2007).…”

Estradiol-mediated protection against high-fat diet induced anxiety and obesity is associated with changes in the gut microbiota in female mice

“…Postmenopausal women experience an increased rate of depressive and anxious mood [17][18][19][20] , particularly during the onset of menopause, that is ameliorated by hormone replacement therapy [21][22][23] . Similarly, ovariectomy in rodents increases depressive-and anxiety-like behavior [24][25][26][27] , while physiological doses of E decrease anxiety-like behavior in ovariectomized rodents, indicating that estrogens have anxiolytic effects in females 28,29 . Estrogen receptor (ER)-specific effects have been demonstrated using ERα and ER β knockout mice or receptorspecific agonists, which have shown ERβ as a primary mediator of anxiety behavior in females [30][31][32] .The lower gastrointestinal (GI) tract is inhabited by a collection of bacteria, viruses, archaea, protozoa, and fungi, known as the gut microbiota 33 .…”

Sex Differences in Behavior and Learning Abilities in Adult Rats

“…It seems likely that females lost their weight during the first test day because of increased locomotion (or behavioral excitation), reflecting curiosity. It is known that female rodents are characterized by a higher curiosity and higher locomotor activity in a novel environment than males [ 51 , 52 , 53 ]. A temporal increase in locomotion might cause a decrease in female body weight.…”