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Estrogen mediates sex differences in stress-induced prefrontal cortex dysfunction
R M Shansky1, C Glavis-Bloom, D Lerman
1Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520-8001, USA. rebecca.shansky@yale.edu
Molecular Psychiatry
|October 22, 2003
Summary
Estrogen amplifies stress effects on the prefrontal cortex (PFC), potentially explaining why women experience higher rates of anxiety and major depressive disorder (MDD). This study highlights sex differences in stress-induced PFC dysfunction.
Area of Science:
- Neurobiology
- Psychiatry
- Endocrinology
Background:
- Anxiety disorders and major depressive disorder (MDD) are twice as common in women as men.
- The neurobiological underpinnings of this sex disparity are not well understood.
- Prefrontal cortex (PFC) dysfunction is linked to MDD and stress exposure.
Purpose of the Study:
- To investigate sex differences in stress-induced PFC dysfunction.
- To examine the role of estrogen in stress sensitivity within the PFC.
Main Methods:
- Male and female rats were tested on a PFC-dependent working memory task.
- FG7142, a stress-activating agent, was administered.
- Experiments included different phases of the female rat estrous cycle and ovariectomized females with estrogen replacement.
Main Results:
- Female rats showed impaired working memory at lower FG7142 doses than males during proestrus (high estrogen).
- No significant sex difference in impairment was observed during estrus (low estrogen).
- Ovariectomized females only exhibited heightened stress sensitivity after estrogen replacement.
Conclusions:
- Estrogen appears to enhance stress-induced PFC dysfunction.
- This estrogen-mediated effect may contribute to the higher prevalence of stress-related disorders in women.
- Findings suggest a neurobiological basis for sex differences in susceptibility to MDD and anxiety.