Elsevier

Neuroscience

Volume 113, Issue 2, 12 August 2002, Pages 401-410
Neuroscience

Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats

https://doi.org/10.1016/S0306-4522(02)00156-2Get rights and content

Abstract

Twenty-one days of chronic restraint stress impairs male rat performance on the radial arm maze [Luine et al. (1994) Brain Res. 639, 167–170], but enhances female rat performance [Bowman et al. (2001) Brain Res. 904, 279–289]. To assess possible ovarian hormone mechanisms underlying this sexually dimorphic response to stress, we examined chronic stress effects in ovariectomized rats. Ovariectomized rats received Silastic capsule implants containing cholesterol or estradiol and were assigned to a daily restraint stress (21 days, 6 h/day) or non-stress group. Following the stress period, subjects were tested for open field activity and radial arm maze performance. Stress and estradiol treatment affected open field activity. All stressed animals, with or without estradiol treatment, made fewer total outer sector crossings. In contrast, estradiol-treated animals, with or without stress, made more inner sector visits, an indication that estradiol decreased anxious behavior on the open field across time. As measured by the total number of visits required to complete the task, stress did not affect radial arm maze performance in ovariectomized rats, but estradiol-treated animals, with or without stress, performed better than non-treated animals on the radial arm maze. Stressed subjects receiving estradiol showed the best radial arm maze performance. Following killing, tissue samples were obtained from various brain regions known to contribute to learning and memory, and monoamine and metabolite levels were measured. Several changes were observed in response to both stress and estradiol. Most noteworthy, stress treatment decreased homovanillic acid levels in the prefrontal cortex, an effect not previously observed in stressed intact females. Estradiol treatment increased norepinephrine levels in CA3 region of the hippocampus, mitigating stress-dependent changes. Both stress and estradiol decreased dentate gyrus levels of 5-hydroxyindole acetic acid.

In summary, the current study provides novel information showing that estradiol alters behavioral and neurochemical responses to stress in ovariectomized rats. Estradiol treatment decreased anxious behavior on the open field and stressed animals receiving estradiol had enhanced radial arm maze performance. In relation to interactions between stress and estradiol on cognition and anxiety, changes in the prefrontal cortex dopaminergic system, dentate gyrus serotonergic system, and norepinephrine levels in the CA3 region appear important. Results show that estradiol may moderate stress effects on cognition and anxiety through both organizational and activation effects.

Section snippets

Subjects

Thirty-two female Sprague–Dawley rats (Harlan Sprague–Dawley, Indianapolis, IN, USA) aged 55–60 days old (upon arrival) served as subjects. All animals were maintained on a 14/10-h light/dark cycle (lights on at 05:00 h) and in accordance with the NIH Guide for Care and Use of Animals. Animals were allowed to acclimate to the housing environment for two weeks. During the acclimation period and the 21-day stress period, all subjects were double housed in plastic tubs. All animals were weighed

Weight

Animal weight gain was affected by stress (F1,92=16.72, P<0.0001), estradiol (F1,92=188.40, P<0.0001), and time (F1,92=34.98, P<0.0001). Weight gain across the daily restraint period was also influenced by the stress×time interaction (F4,92=2.88, P<0.03) and the estradiol×time interaction (F4,92=9.23, P<0.0001). As seen in Fig. 1, stressed animals weighed less than the non-stress and estradiol-treated females weighed less than their cholesterol controls across the stress period.

Open field

Open field

Body weight

All animals used in this study gained weight across time; however, the weight gain differed among the treatment groups. Stressed females gained less weight than non-stress females across the 21 days and this is consistent with previous studies in which both stress and CORT administration led to decreases in body weight (McLay et al., 1998, Beck and Luine, 1999, Akana et al., 1999, Bowman et al., 2001). Additionally, all estradiol-treated females weighed less than their cholesterol counterparts,

Acknowledgements

Financial support for this work was provided by NRSA 1F31MH12515 to R.E.B. and Hunter College MARC, RISE, and RCMI grants (NIGMS). We extend our appreciation to Dr. Sosimo Fabian for critical review of the manuscript and Dr. Mark Zrull for statistical consultation.

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