Influence of the post-ovariectomy time frame on the experimental anxiety and the behavioural actions of some anxiolytic agents (original) (raw)
Related papers
Journal of Pharmacy and Pharmacology 5 (2017) 869-876, 2017
On study of the effects of estrogen deficiency on anxiety disorder by using ovariectomised animals, one discrepancy was the difference in behavioral testing delay following ovariectomy and the paradigms used. Thus, the aim of this study was to evaluate the anxiogenic effects of fourteen-day estrogen decline subsequent to ovariectomy on Wistar rats using EPM (elevated plus-maze) and open field tests. As results, fourteen days of estrogens decline has induced an increase of anxiety-related behaviour by a reduction of the percentage of the number of entries into the open arm (p < 0.01) and an increase of the percentage of the number of entries into the closed arm (p < 0.01) during the elevated plus-maze test. This anxiety-like behaviour was confirmed on the open field test by a reduction of time spent in the centre of the arena (p < 0.05) as well as a reduction of crossing (p < 0.05) and an increase of the weight of faecal boli (p < 0.05) and grooming (p < 0.01). Meanwhile, the administration of diazepam or estradiol valerate (1 mg/kg BW each) has corrected the anxious-like behaviour in both tests paradigms. These results suggest that fourteen days of estrogens decline was associated with an anxiety-related behaviour. This experimental model can constitute an excellent tool for the study of anxiolytic substances in menopause-related anxiety.
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.
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
Pharmacology Biochemistry and Behavior, 1999
FERNÁNDEZ-GUASTI, A., L. MARTÍNEZ-MOTA, E. ESTRADA-CAMARENA, C. M. CONTRERAS AND C. LÓPEZ-RUBALCAVA. Chronic treatment with desipramine induces an estrous cycle dependent anxiolytic-like action in the burying behavior, but not in the elevated plus-maze test. PHARMACOL BIOCHEM BEHAV 63 (1) 13-20, 1999.-The effect of chronic desipramine (DMI, 2.5 mg/kg ϫ 21-26 days) treatment in female rats in two anxiety paradigms was assessed: the burying behavior (BB) and the elevated plus-maze (EPM) tests. In the BB test DMI produced a significant decrease in burying in ovariectomized rats, an effect considered as anxiolytic-like. In cycling females, DMI also reduced the cumulative BB most notably in proestrus rats. However, in diestrus rats no anxiolytic-like actions were observed. In addition, DMI increased BB latencies in proestrus and estrus rats. In the EPM test, DMI produced anxiolytic-like actions only in ovariectomized rats, while no significant actions were found in cycling females. Finally, the chronic treatment with DMI produced a general reduction in the ambulatory behavior of rats in all estrous cycle phases. Results are discussed on the basis of the differences between both anxiety paradigms and the probable relationship between the steroids secreted during proestrus and chronic DMI treatment.
Parity and estrogen-administration alter affective behavior of ovariectomized rats
Physiology & Behavior, 2008
Evidence from clinical and basic research studies demonstrates that estradiol (E 2) reduces anxiety and/or depressive behavior; however, this effect is not observed in all studies. One factor that may mitigate differential responses to E 2 may be previous E 2 experience, i.e. parity. To investigate this, performance in tasks that are utilized to assess whether compounds, such as E 2 , can alter anxietylike behavior (elevated plus maze) and have anti-depressant-like effects (forced swim test) were determined. Performance of ovariectomized (ovx), young (3-6 months old) rats that had never had a litter (nulliparous) was compared to that of those that had several litters in their lifetime (multiparous) following 48 h of oil vehicle or E 2 (10 µg) administration. We predicted that E 2 would decrease anxiety-like behavior and increase anti-depressant-like effects of ovx rats and that this pattern may be influenced by parity. Multiparous rats, irrespective of E 2-priming, had increased open arm time compared to nulliparous rats. Administration of E 2 to ovx, nulliparous or multiparous rats decreased immobility in the forced swim test compared to vehicle-administration. Together, these data suggest that E 2 can alter affective behavior and rats with greater reproductive experience have decreased anxiety-like behavior in the elevated plus maze, irrespective of E 2-priming.
Modulation of anxiety behavior in gonadectomized animals
Acta Neurobiologiae Experimentalis
Anxiety is a complex psychological state which happens after stressful life experiences. Many factors such as daily life events, neurotransmitter systems, and different brain areas could influence anxiety behavior in humans and animals. For example, opioids and androgens decrease anxiety behavior both in humans and animals. Furthermore, removing the testes (gonadectomy) causes higher levels of anxiety-like behaviors, in which the administration of testosterone and opioid antagonist can reverse some of these behaviors. We review the effects of morphine and androgens on the modulation of anxiety behavior in gonadectomized animals. We begin by highlighting the effects of opioid drugs and androgens on the modulation of anxiety behavior that have been implicated in anxiety behavior. We then discuss the functional consequences of gonadectomy on anxiety behavior. Finally, we consider how the opioids and androgens may contribute to adaptive responses associated with anxiety.
Hormones and Behavior, 2010
Ovarian hormones exert anti-depressive and anxiolytic actions. In this study we have analyzed the effects of ovariectomy on the development of anxiety and depression-like behaviors and on cell proliferation in the hippocampus of mice submitted to chronic unpredictable stress. Animals submitted to stress 4 months after ovariectomy showed a significant increase in immobility behavior in the forced swimming test compared to animals submitted to stress 2 weeks after ovariectomy. In addition, long-term ovariectomy resulted in a significant decrease on the time spent in the open arms in the elevated plus-maze test compared to control animals. Stress did not significantly affect cell proliferation in the hilus of the dentate gyrus. However, ovariectomy resulted in a significant decrease in cell proliferation. These results indicate that long-term deprivation of ovarian hormones enhances the effect of chronic unpredictable stress on depressive-and anxiety-like behaviors in mice. Therefore, a prolonged deprivation of ovarian hormones may represent a risk factor for the development of depressive and anxiety symptoms after the exposure to stressful experiences.
The effects of diazepam on the elevated T-maze are depended on the estrous cycle of rats
2009
In order to determine the modulation of anxiolytic and panicolytic-like effects of diazepam by the hormonal cycle of female rats, male and female rats-the latter divided per estrous cycle phase (estrus, diestrus, metaestrus and proestrus)-were tested in the elevated T-maze, a behavioral model of panic and anxiety. Diazepam (0.5, 1.0 and 2.0 mg/kg) or saline solution was injected in individual animals that were submitted to one session in the elevated T-maze 25 min after drug/saline administration. The test consisted of three avoidance trials and one escape trial, separated by a 30 s interval, during which the animals were isolated in individual cages. The avoidance trials began with the animal being placed at the end of the maze's enclosed arm. The time necessary for the animal to leave the central square was considered as the response's latency. The trials that exceeded 300 s were considered as failures. Results demonstrate a decrease in the effects of diazepam in inhibitory avoidance (anxiety) trials in females in diestrus and proestrus, but no relation of gender or estrous cycle on diazepam effects on escape trials (fear). The results support the hypothesis that down-regulation of GABA A receptors by activation of nuclear estrogen receptors and induction of PKC-mediated GABA A receptor phosphorylation by activation of surface estrogen receptors in raphe neurons underlie the modulation of diazepam sensitivity by estrogen.
The effects of diazepam on the elevated T-maze are dependent on the estrous cycle of rats
In order to determine the modulation of anxiolytic and panicolytic effects of diazepam by the hormonal cycle of female rats, male and female rats – the latter divided per estrous cycle phase (estrus, diestrus, metaestrus and proestrus) – were tested in the elevated T-maze, a behavioral model of panic and anxiety. Diazepam (0.5, 1.0 and 2.0 mg/kg) or saline solution was injected in individual animals that were submitted to one session in the elevated T-maze 25 min after drug/saline administration. The test consisted of three avoidance trials and one escape trial, separated by a 30 s interval, during which the animals were isolated in individual cages. The avoidance trials began with the animal being placed at the end of the maze's enclosed arm. The time necessary for the animal to leave the central square was considered as the response's latency. The trials that exceeded 300 s were considered as failures. Results demonstrate a decrease in the effects of diazepam in inhibitory avoidance (anxiety) trials in females in diestrus and proestrus, but no relation of gender or estrous cycle on diazepam effects on escape trials (fear). The results support the hypothesis of down-regulation of GABAA receptors by activation of nuclear estrogen receptors and induction of PKC-mediated GABAA receptor phosphorylation by activation of surface estrogen receptors in raphe neurons underlie the modulation of diazepam sensitivity by estrogen.
Journal of Psychopharmacology
Background and aims: We sought a robust behavioural test that evoked increased anxiety-like behaviour during the late dioestrus phase of the oestrous cycle (similar to the premenstrual period in women) and tested whether this could be prevented by acute low-dose fluoxetine (FLX). Methods: Female Wistar rats in different stages of their cycle were exposed to four different tests of anxiety-like behaviour. Results: No oestrous cycle differences were detected in fear potentiated startle or conditioned freezing to an aversive context. In a light switch-off test where rats move from one compartment of a shuttle-box to the other to turn off an aversive light, females displayed enhanced responding in late dioestrus. During isolation restraint stress females in late dioestrus emitted three times more 22 kHz ultrasound vocalisations (USV) than at other cycle stages. Using the USV test, short-term administration of low-dose FLX (1.75 mg kg−1, i.p.) designed to blunt the sharp fall in brain al...