Long-term ovariectomy enhances anxiety and depressive-like behaviors in mice submitted to chronic unpredictable stress (original) (raw)
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Behavioural brain research, 2016
Molecular mechanisms of depression-like pathophysiology in female rodent models are less reported compared to males, despite its higher prevalence in human females. Moreover, the stress-response in brain circuitries including reward and cognition circuitries varies with age or hormonal status of the females. So, to understand the stress-induced mood and cognitive disorders in intact females (with ovaries) and ovariectomized (OVX) females, we studied changes in mouse hippocampus, a functionally heterogeneous neural structure involved in both affective and cognitive behaviors. Here, we used a 6-day Chronic Unpredictable Stress (CUS) paradigm in mice to induce depression and related mood disorders. Interestingly, intact females and OVX females showed difference in mood disorder sub-phenotypes to CUS. Similar to an earlier report of CUS affecting the critical reward circuitry structure the nucleus accumbens differently in females with and without ovaries, cognitive behavior in intact fe...
Ovariectomy results in inbred strain-specific increases in anxiety-like behavior in mice
Physiology & behavior, 2016
Women are at an increased risk for developing affective disorders during times of hormonal flux, including menopause when the ovaries cease production of estrogen. However, while all women undergo menopause, not all develop an affective disorder. Increased vulnerability can result from genetic predisposition, environmental factors and gene by environment interactions. In order to investigate interactions between genetic background and estrogen depletion, we performed bilateral ovariectomy, a surgical procedure that results in estrogen depletion and is thought to model the post-menopausal state, in a genetically defined panel of 37 inbred mouse strains. Seventeen days post-ovariectomy, we assessed behavior in two standard rodent assays of anxiety- and depressive-like behavior, the open field and forced swim tests. We detected a significant interaction between ovariectomy and genetic background on anxiety-like behavior in the open field. No strain specific effects of ovariectomy were ...
Malaysian Journal of Medical Sciences, 2013
Abstract: Background: Depression is one of the common post-menopausal symptoms. In addition to estrogen deficiency, social instability stress may contribute as an additional underlying factor in the development of depressive behaviour in females. Therefore, this study was aimed at examining the influence of social instability stress on depressive behaviour in ovariectomized rats. Methods: The rats were divided into four groups (n = 5 per group); (i) sham-operated control without stress, (ii) sham-operated control with stress, (iii) ovariectomized without stress, and (iv) ovariectomized with stress. These rats were subjected to social instability stress procedures for 15 days prior to an enforced swimming test. Struggling, immobility, and swimming times were recorded promptly. Results: The results were analysed using the one-way analysis of variance (ANOVA) and a P value of < 0.05 was considered as significant. The mean durations of struggling, immobility, and swimming behaviour were significantly distinct among the four groups. Ovariectomized rats exhibited a substantial decrease in struggling and swimming behaviour, and an increase in immobility behaviour in comparison with the sham-operated controls (P < 0.05). Ovariectomized rats with stress displayed a supplementary decrease in struggling and swimming behaviour as well as an advanced increase in immobility behaviour, compared to sham-operated controls with or without stress (P < 0.05). Conclusion: In summary, these findings suggest that ovariectomized rats encountered an augmented amount of depressive behaviour following social instability stress.
Mood and Memory Function in Ovariectomised Rats Exposed to Social Instability Stress
BioMed Research International, 2013
This study aims to compare the effects of social instability stress on memory and anxiety- and depressive-like behaviour between sham-operated controls and ovariectomised (OVX) rats. Forty adult female Sprague-Dawley rats (8 weeks old) were randomly divided into four groups, (n = 10 per group). These were non-stressed sham-operated control rats, stressed sham-operated control rats, non-stressed OVX rats, and stressed OVX rats. The rats were subjected to social instability stress procedure for 15 days. Novel object recognition, open field, and forced swim tests were conducted after the stress procedure. Serum estradiol, ACTH and corticosterone levels were measured using commercially available ELISA kits. Lower serum estradiol level and uterine weight with higher weight gain were observed in OVX rats compared to sham-operated controls. Serum ACTH, and corticosterone levels were higher in stressed compared to non-stressed groups. Memory deficit and anxiety- and depressive-like behaviour were significantly increased in stressed compared to non-stressed OVX rats but these changes were not seen in sham-operated controls. These results suggest that the high circulating corticosterone acts synergistically with low circulating estradiol to exert negative effects on mood and memory function.
Neuroscience, 2017
Depression induced by stress is affected by sex, age and hormonal status of the animal and also by duration and type of the stressors. Moreover, higher prevalence of depression and comorbidities in women than men implies the need to include the sex variable in studies on animal models of depression. The present study was therefore initiated to evaluate the effect of sex and ovarian hormones on depression-like phenotypes in mice exposed to a 21-day Chronic Variable Mild Stress (CVMS) paradigm. Adult male, intact female and, ovariectomized (OVX) female mice exposed to CVMS displayed despair behavior, a depression-like phenotype, in all the groups. However, intact females alone, but not males and OVX females, showed anhedonia, another depression-like phenotype. At the molecular level, the expression of Brain-Derived Neurotrophic Factor (BDNF), a neuropeptide associated with depression, and few other stress-specific genes CRH, NR3C1, CART, and NPY were measured in the Prefrontal Cortex ...
European Journal of Pharmacology, 2006
This study analyzes the long-term effects of ovariectomy on the basal experimental anxiety of rats and the influence of this condition on the anxiolytic properties of diazepam and the 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Rats ovariectomized 3, 6 and 12 weeks previously, were tested in the burying behaviour paradigm and in an automatic activity counter. The highest values of time spent burying were observed in the 12-week group. In general, the 12-week group was more responsive to diazepam than the 3-week group, while 8-OH-DPAT showed similar effects on time spent burying, independently of how long ago the ovariectomy was done.
Hippocampus, 2013
The peripartum period is a time of high susceptibility for mood and anxiety disorders, some of which have recently been associated with alterations in hippocampal neurogenesis. Several factors including stress, aging, and, perhaps unexpectedly, lactation have been shown to decrease hippocampal neurogenesis. Intriguingly, lactation is also a time of reduced stress responsivity suggesting that the effect of stress on neurogenic processes may differ during this period. Therefore, the aim of the present study was to assess the effect of repeated stress during lactation [2 h restraint stress from lactation day (LD) 2 to LD13] on brain weight, hippocampal volume, cell proliferation and survival, and on neuronal and astroglial differentiation. In addition to confirming the known lactationassociated decrease in cell proliferation and survival, we could reveal that stress reversed the lactation-induced decrease in cell proliferation, while it did not affect survival of newly born cells, nor the number of mature neurons , nor did it alter immature neuron production or the number of astroglial cells in lactation. Stress exposure increased relative brain weight and hippocampal volume mirroring the observed changes in neurogenesis. Interestingly, hippocampal volume and relative brain weight were lower in lactation as compared to nulliparous females under nonstressed conditions. This study assessed the effect of stress during lactation on hippocampal neurogenesis and indicates that stress interferes with important peripartum adaptations at the level of the hippocampus. V C 2014 Wiley Periodicals, Inc.