Related Experiment Video
Updated: Aug 7, 2026
Exploring Independent Effects of Follicle-Stimulating Hormone In Vivo in a Mouse Model
Published on: August 11, 2023
Factors producing a menopausal depressive-like state in mice following ovariectomy
Naoko Bekku1, Hiroyuki Yoshimura, Hiroaki Araki
1Department of Pharmacology and Pharmacy, Ehime University Graduate School of Medicine, Shitsukawa, Toon-City, Ehime 791-0295, Japan.
Rationale:
Bilateral ovariectomy in female mice produces a menopausal depressive-like state but the factors responsible for the phenomenon are unknown.
Objectives:
We elucidated methodological issues related to establishing this mouse model and investigated a possible mechanism underlying the depressive-like state of ovariectomized mice.
Methods:
We removed both ovaries of female ICR mice at 9 weeks of age. Changes in the immobility time during the forced swimming test as a function of the time interval between ovariectomy and behavioral testing were determined on nine different days after surgery. To assess behavioral specificity, the elevated plus-maze (EPM) behavior and spontaneous activity were measured. With respect to the effect of ovariectomy on the immobility time, we compared ICR mice with three other strains of mice (C57BL/6J, DBA/2N, and CD-1). Finally, we investigated the effects of (-)-2,5-dimethoxy-4-iodoamphetamine (DOI) and (+/-)-8-hydroxy-2-(N,N-di-n-propylamino) tetralin (8-OH-DPAT) on the immobility time of ovariectomized mice.
Results:
A significant effect on the prolongation of immobility was observed between 12 and 18 days after ovariectomy. Ovariectomy did not alter either the EPM behavior or spontaneous activity. Of the four strains of mice, only DBA mice did not show any significant prolongation of immobility after ovariectomy. Acute or chronic treatment with DOI (0.5 or 1.0 mg kg(-1)) significantly prevented the prolongation of immobility time, whereas acute and chronic treatments with 8-OH-DPAT (0.05, 0.5, or 1.0 mg kg(-1)) were ineffective.
Conclusion:
The present findings have potentially important implications for evaluating a candidate substance for the management of mood disorders in menopausal women.
Insights
Bilateral ovariectomy in mice creates a menopausal depressive-like state. The drug DOI, but not 8-OH-DPAT, effectively reversed this state, offering insights for mood disorder treatments.
Area of Science:
- Neuroscience
- Pharmacology
- Animal Models
Background:
- Bilateral ovariectomy in female mice induces a menopausal depressive-like state.
- The specific factors contributing to this induced state remain unidentified.
Purpose of the Study:
- To address methodological challenges in establishing the ovariectomy-induced mouse model of depression.
- To investigate potential mechanisms underlying the depressive-like state observed in ovariectomized mice.
Main Methods:
- Ovariectomy was performed on female ICR mice at 9 weeks of age.
- Behavioral tests, including forced swimming and elevated plus-maze, were conducted at various time points post-surgery.
- The effects of DOI and 8-OH-DPAT on immobility were assessed in ovariectomized mice.
Main Results:
- A significant increase in immobility time was observed 12-18 days post-ovariectomy.
- Ovariectomy did not affect elevated plus-maze behavior or spontaneous activity.
- DOI treatment attenuated the ovariectomy-induced immobility, while 8-OH-DPAT was ineffective.
Conclusions:
- The findings provide a validated mouse model for studying menopausal depression.
- DOI shows potential as a therapeutic agent for mood disorders in menopausal women.
- This research has implications for developing treatments for mood disturbances associated with menopause.
More Related Videos
14:26A Method to Study the Impact of Chemically-induced Ovarian Failure on Exercise Capacity and Cardiac Adaptation in Mice
Published on: April 7, 2014
06:18An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
