Stress-induced sensitization of the limbic system in ovariectomized rats is partly restored by cyclic 17 beta-estradiol administration

Marjolein Gerrits, Petra L. Bakker, T Koch, Gert J. Ter Horst

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    21 Citations (Scopus)

    Abstract

    Chronic stress induces neurobiological alterations which have consequences for subsequent stress handling. In the current experiment, ovariectomized rats were subjected daily to a stressor for 21 days. Thereafter, the rats were treated for 21 days with 17 beta-estradiol benzoate (10 mu g/250 g, once every 4 days) or mirtazapine (10 mg/kg, daily). In this way, we were able to evaluate the ability of these compounds to reverse chronic stress-induced changes in the activity of the limbic system. After 21 days of recovery and treatment, the rats were re-exposed to the adverse environment of the initial stressor and perfused 2 h later. Ovariectomized rats displayed increased numbers of c-Fos-positive nuclei, after re-exposure to the stressor, in the paraventricular nucleus of the hypothalamus, dentate gyrus, medial prefrontal cortex and central and medial amygdala. Cyclic estradiol treatment attenuated the sensitization of the paraventricular nucleus and central amygdala. Mirtazapine increased the number of c-Fos-positive nuclei in the central amygdala and dentate gyrus. Long-term transcriptional changes induced by chronic stress were determined with Delta FosB immunoreactivity. The medial prefrontal cortex showed an increased number of Delta FosB-positive nuclei after chronic stress and this was not affected by estradiol or mirtazapine administration during recovery. In conclusion, cyclic estradiol administration reversed chronic stress-induced sensitization in the limbic system, the paraventricular nucleus and central amygdala of female rats, output regions of the limbic system involved in fear responses. Mirtazapine did not achieve this of stress-induced aberrations in the limbic system after 21 days of treatment.

    Original languageEnglish
    Pages (from-to)1747-1756
    Number of pages10
    JournalEuropean Journal of Neuroscience
    Volume23
    Issue number7
    DOIs
    Publication statusPublished - Apr-2006

    Keywords

    • affective disorders
    • c-Fos
    • Delta FosB
    • mirtazapine
    • PVN
    • LONG-TERM TREATMENT
    • C-FOS EXPRESSION
    • MEDIAL PREFRONTAL CORTEX
    • CHRONIC RESTRAINT STRESS
    • CENTRAL-NERVOUS-SYSTEM
    • GENE-EXPRESSION
    • SEX-DIFFERENCES
    • DELTA-FOSB
    • ANTIDEPRESSANT DRUGS
    • POSTMENOPAUSAL WOMEN

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