Short-term, low-dose fluoxetine prevents oestrous cycle-linked increase in anxiety-like behaviour in female rats (original) (raw)
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Effects of the estrous cycle and ovarian hormones on behavioral indices of anxiety in female rats
Psychoneuroendocrinology, 1996
The influence of the estrous cycle and the effects of exogenous administration of estradiol and progesterone on level of anxiety were studied in intact and ovariectomized rats. Intact Sprague-Dawley female rats were classified according to the stages of estrous cycle. Another group of rats was ovariectomized bilaterally and, 14 days after surgery, they received estradiol benzoate (10/~g/kg, SC) and/or progesterone (25 mg/kg, SC) or corn oil (1 ml/kg). The behavioral tests began 3 h after estradiol or 6 h after progesterone and consisted of: (1) exploration of an elevated plus-maze; and (2) retention of a passive avoidance response. Open-arm exploration of the plus-maze varied according to light intensity and the stages of the estrous cycle. There was a slight increase in open-arm exploration by rats in metestrus, under high light intensity. Low light intensity increased the exploration of the open arms by rats in proestrus and estrus, compared to the other phases of the cycle. Retention of the passive avoidance response was inhibited during proestrus and estrus. Progesterone increased openarm exploration of the plus-maze under high light conditions, whereas estradiol antagonized this effect. Retention of passive avoidance was inhibited after estradiol or progesterone injection. These results suggest that the behavioral indices of anxiety can vary across the estrous cycle, that low light intensities have anxiolytic-like effects, and that the sensitivity to this effect is higher during proestrus and estrus. This could be explained through modulatory effects of ovarian hormones upon behavioral indices of anxiety.
Subchronic Administration of Fluoxetine Impairs Estrous Behavior in Intact Female Rats
Neuropsychopharmacology, 1998
Treatment with serotonin reuptake inhibitors (SRIs) has been shown to cause reduced libido and anorgasmia in women. A large body of evidence suggests that serotonin may influence sexual behavior in estradiol ϩ progesterone primed, gonadectomized female rats; however, the influence of selective SRIs on the estrous behavior of intact female rats has not been described previously. In the present study, the effect of 1 to 3 weeks of fluoxetine administration (10 mg/kg daily) on vaginal and behavioral estrus in intact female rats was studied; in addition, the effect of fluoxetine (same dose, 1-8 weeks) on copulatory behavior and on sexual motivation in hormone-primed gonadectomized rats was investigated. Subchronic administration of fluoxetine did not influence cyclicity as judged by the examination of vaginal smears but significantly reduced the percentage of rats displaying receptive behavior in the estrous phase. In addition, fluoxetine significantly reduced receptive behavior, including lordosis, in ovariectomized female rats primed with estradiol (6.25 g/rat; Ϫ 48 hr) plus progesterone (1.0 mg/rat, Ϫ 4 hr); in contrast, sexual motivation-as reflected by the amount of time these rats elected to spend in the vicinity of a male rather than in the vicinity of a female or elsewhere-was little affected by the treatment.
Neuropsychopharmacology, 2001
The aggressive behavior displayed by some (but not all) female Wistar rats when an unfamiliar rat is being introduced into their home cage (the resident intruder paradigm) was found to be higher in non-receptive phases (metestrus, diestrus) than in the receptive phases (proestrus, estrus) of the estrus cycle, and effectively reduced by ovariectomy. When removal of the ovaries was followed by administration of estradiol and progesterone, in a regimen mimicking the normal cyclical release of these hormones, aggressive behavior was elicited, two days after estrus, in animals that had displayed aggressive behavior before ovariectomy, but not in those that had not. Short-term administration of a serotonin reuptake inhibitor (fluoxetine hydrochloride; 10 mg/kg, i.p.; 4-5 days) reduced both the aggressive behavior displayed during the diestrus phase by normally cycling rats, and the aggressive behavior elicited by administration of estradiol plus progesterone after ovariectomy. It is suggested that the aggressive behavior displayed by the female Wistar rat in the resident intruder paradigm may serve as an animal model of premenstrual dysphoria.
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.
Brain Research, 2008
In an earlier study, we reported that daily fluoxetine treatment (10 mg/kg/day) rapidly disrupted estrous cyclicity and sexual receptivity in adult, regularly cycling Fischer rats. The current study was designed to investigate if comparable fluoxetine treatment would similarly affect intact, regularly cycling Sprague Dawley rats. In the first experiment, fluoxetine was injected for 24 days. After 11-14 days of daily fluoxetine treatment, 40% of the rats showed a transient disturbance of the estrous cycle with elimination of sexual receptivity. In these affected rats, reduced sexual receptivity generally preceded disruption of vaginal cyclicity. In a second experiment, a shorter exposure was used to attempt to dissociate effects of fluoxetine on behavior and estrous cyclicity. Nine days of fluoxetine treatment eliminated sexual receptivity and proceptivity (hops/darts) in 40% and 46%, respectively, of rats without altering the estrous cycle. Female rats then received a 10 th fluoxetine injection 30 min prior to assessment of sexual motivation (measured with the male preference paradigm). There was no effect of fluoxetine on male preference, but fluoxetine significantly reduced the number of crossings and seconds of grooming during preference testing. Therefore, effects of fluoxetine on estrous cyclicity and behavior of Sprague Dawley female rats were smaller and required longer to develop than previously reported in Fischer female rats. These findings reinforce a probable relationship between fluoxetine's effect on sexual activity and neuroendocrine disturbances and illustrate the importance of strain selection in attempting to model human disease.
Translational Psychiatry
Fluctuations in ovarian steroids across the estrous and menstrual cycle in female rats and women, respectively, are associated with changes in anxiety. Pregnancy causes long-term changes to ovarian hormone release, yet research on estrous- and menstrual-related changes in anxiety has focused on reproductively inexperienced females. Therefore, this study assessed whether the impact of estrous and menstrual cycles on anxiety differs pre- versus post-motherhood in female rats (n = 32) and a community sample of women (n = 63). Estrous cycle phase altered anxiety-like behavior in virgin rats, but had no effect in age-matched mother rats tested 1-month post-weaning. In humans, menstrual cycle phase was associated with ecological momentary assessed anxiety and mood in non-mothers, but not mothers; although, the menstrual cycle × reproductive status interaction for anxiety, but not mood, was rendered non-significant with age and cycle length as covariates. These findings suggest that change...
2020
In this research, the changes of anxiety and blood progesterone levels during the oestrus cycle were studied in rats genetically selected for high (KHA) and low (KLA) acquisition of active avoidance. Anxiety levels were measured by the time spent in open arms of the elevated plus-maze. Progesterone levels were determined by radioimmunoassay. KLA rats exhibited no significant changes in anxiety levels during the oestrus cycle. KHA rats showed a significant variation of anxiety during the oestrus cycle with a high level in the diestrus phase and a low level in proestrus. Moreover, anxiety in diestrus in KHA rats was higher than in KLA rats. Additionally, increased progesterone levels were observed in KLA rats in comparison with the KHA strain, during both diestrus and proestrus. Anxiety levels corresponded to plasma progesterone during the oestrus cycle in both rat strains.
2018
Some mood disorders, such as major depressive disorder, are more prevalent in women than in men. However, historically preclinical studies in rodents have a lower inclusion rate of females than males, possibly due to the fact that behavior can be affected by the estrous cycle. Several studies have demonstrated that chronic antidepressant treatment can decrease anxiety-like behaviors and increase adult hippocampal neurogenesis in male rodents. However, very few studies have conclusively looked at the effects of antidepressants on behavior and neurogenesis across the estrous cycle in naturally cycling female rodents. Here we analyze the effects of chronic treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac) on behavior and adult hippocampal neurogenesis in naturally cycling C57BL/6J females across all four phases of the estrous cycle. Interestingly, we find that the effects of fluoxetine on both behavior and adult hippocampal neurogenesis are driven by ...
Female fear: Influence of estrus cycle on behavioral response and neuronal activation
Behavioural Brain Research, 2009
Our observation that male rats innate fear response differed with hormonal status, as well as the higher prevalence of fear and anxiety disorders in human females led to the current investigation of the impact of phases of the estrous cycle on innate fear responding. Female rats in different phases of the cycle were exposed to an innate fear-inducing stimulus (2,5-dihydro-2,4,5-trimethylthiazoline, TMT odor) and monitored for changes in behavior and brain activation. Behavioral data showed freezing responses to TMT were significantly enhanced during estrus as compared to other phases of the cycle. This data was supported by significant increases in pixel intensity in cortical and subcortical regions in estrus compared to proestrus and diestrus.
Hormones and Behavior, 2004
Estrogen may have differing effects on 'anxiety' responses under different conditions. The current study tested the effects of estrogen on anxiety-like behavior when administered for 6 -7 days in ovariectomized (OVX) female rats. Two animal paradigms were utilized; the elevated plus maze (EPM), measuring changes in innate fear of exploration of open spaces; and the social interaction test (SIT), measuring the exploration of a novel, same gender partner. In the EPM, estradiol-treated OVX females both entered and spent more time in the open arms than control OVX females, indicating an anxiolytic-like action of estradiol. In contrast, estradiol treated OVX females interacted less with the partner animal in the SIT compared with controls suggesting anxiogenic-like effects. The possible anxiogenic effect of estradiol in the SIT is supported by two findings: (1) the effect is reversed by the anxiolytic drug alprazolam and (2) estrogen did not affect locomotion and therefore, the reduced social interaction is not due to reduced activity. Acute administration of progesterone (5 mg/kg), which has anxiolytic properties, did not reverse estradiol-induced social interaction deficits, suggesting that lack of progesterone did not account for estradiol's anxiogenic effects. These results, while seemingly contradictory when interpreted within a unified concept of anxiety, may well reflect the ethological roles of reproductive hormones and their effects on different types of exploratory anxiety. D