Nelson Dussaubat

Effects of the estrous cycle and ovarian hormones on behavioral indices of anxiety in female rats

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 micrograms/kg, s.c.) and/or progesterone (25 mg/kg, s.c.) 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 open-arm 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.

Influence of the estrous cycle, ovariectomy and estradiol replacement upon the acquisition of conditioned avoidance responses in rats☆

The changes in the acquisition of conditioned avoidance responses (CARs) and the performance of some spontaneous behaviors were examined across the estrous cycle of female rats. CARs were facilitated during diestrus, impaired at proestrus and practically abolished at estrus and metestrus. Motor activity and head shaking were minimally affected with the stages of the cycle. Motor activity was increased at metestrus and head shaking decreased at estrus. At 14 days following ovariectomy, there was a significant enhancement of CARs which was antagonized by the daily administration of estradiol benzoate (10 micrograms/kg) for three days. Ovariectomy also increased grooming behavior and estradiol replacement returned grooming to its basal level. The results suggest an inhibitory control of estradiol on CARs and grooming. The involvement of other hormones which also varied across the estrous cycle and its interaction with brain catecholamine systems, particularly dopamine, are discussed.

Ketanserin and anxiety levels : Influence of gender, estrous cycle, ovariectomy and ovarian hormones in female rats

The influence of gender, estrous cycle, ovariectomy and ovarian hormones on the behavioral effects of the 5-HT2 receptor antagonist, ketanserin (KET), was studied. Intact males, female rats in the four stages of the estrous cycle and ovariectomized (OVX) female rats 14 days after surgery were used. The OVX rats received progesterone [PROG, 25 mg/kg, subcutaneously (SC)] and/or estradiol benzoate (EB, 10 micrograms/kg, SC). KET (3 mg/kg, SC) was injected 30 min before testing. All the animals were subjected to the following behavioral tests: exploration of an elevated plus-maze and retention of a passive-avoidance response. KET enhanced the exploration of the open arms in diestrous female rats but inhibited this behavior during the other stages of the cycle and in OVX rats injected either with oil or EB. This dose of KET was ineffective in males and in OVX rats injected with PROG. Furthermore, KET inhibited the retention of the passive avoidance response in males, in diestrous and metestrous female rats and in OVX rats injected with oil. In estrous females and in OVX rats injected with EB, KET enhanced the passive-avoidance response. These results demonstrate that the sensitivity to KET differs with the gender, estrous cycle and hormonal treatment and suggest that central serotonergic activity is influenced by the hormonal status of the animal.

Effects of estradiol replacement in ovariectomized rats on conditioned avoidance responses and other behaviors

The acquisition of conditioned avoidance responses along with spontaneous behaviors were studied in ovariectomized rats. Fourteen days after ovariectomy, they were injected subcutaneously with one of the following doses of estradiol benzoate: 0.2, 2 or 20 microgram/rat. Behavioral tests were applied 3, 24, 48 or 72 hours after estradiol treatment. Although estradiol 2 microgram/rat induced a decrease in acquisition of conditioned avoidance responses at all times tested, this effect was maximum at 48 h. Estradiol 0.2, and 20 microgram/kg decreased and stimulated, respectively, the acquisition performance, as tested 3 h after injection. All doses increased global motility and rearing behavior. This hypermotility disappeared at 24 h, but it was observed again at 48 and 72 h after estradiol 0.2 and 20 microgram/rat. The hormone also induced an increase in head shaking and a decrease in grooming. Although the behavioral changes are more significant in presence of very low serum levels of estradiol, they seem to be triggered by the previous increase in the estradiol levels. The possible sites and mechanisms of action of estradiol on behavior are discussed.

Gender, Estrous Cycle, Ovariectomy, and Ovarian Hormones Influence the Effects of Diazepam on Avoidance Conditioning in Rats

This study examines whether the hormonal condition of the rat modifies the effects of diazepam (0.25 and 1.0 mg/kg) on avoidance conditioning and other behavioral responses. Acquisition of a conditioning avoidance response (CAR) and spontaneous motor behaviors were assessed in intact male, in intact diestrous and estrous females, and in ovariectomized (OVX) rats injected with estradiol (2 microg/rat, SC) or progesterone (5 mg/rat, SC). A higher dose (1.0 mg/kg) of diazepam significantly impaired the acquisition of CARs in diestrous, OVX, OVX + progesterone, and male rats. Conversely, both doses of diazepam significantly improved the acquisition of CAR in estrous rats and in OVX rats injected with estradiol. These effects on conditioning avoidance were not accompanied with equivalent changes in spontaneous motor behaviors. Motor activity and grooming behavior decreased in all experimental groups after administration of 1.0 mg/kg of diazepam. On the contrary, diazepam 0.25 mg/kg increased motor activity in estrous, OVX + estradiol, and OVX + progesterone rats after, whereas grooming behavior was not affected in any group. These findings suggest a physiological influence of ovarian steroid hormones in modifying the benzodiazepine effects on conditioning avoidance and motor activity. The results are discussed considering that ovarian steroids may interact with diazepam on the GABA(A)/benzodiazapine/chloride ionophore complex, modifying the coupling between benzodiazepine sites and GABA(A) receptors.

Progesterone effects on the acquisition of conditioned avoidance responses and other motoric behaviors in intact and ovariectomized rats

This study demonstrates a significant impairment in the acquisition of conditioned avoidance responses in female rats during their estrus phase. Progesterone (PROG 5 mg) injected 6 h prior to the test, significantly enhanced the performance exhibited by rats at estrus, but not at diestrus. In ovariectomized rats, the acquisition of conditioned avoidance responses was similar to the exhibited during diestrus and this behavior was depressed by a single dose of estradiol benzoate (EB 2 micrograms) injected 48 h prior to the test. PROG antagonized the avoidance depression induced by EB, but it was not able to induce changes in the acquisition of conditioned avoidance response in ovariectomized rats without EB pretreatment. Estradiol appears to be the principal ovarian steroid modulating the acquisition of an avoidance task, whereas PROG seems to have a secondary role in this behavior, regulating the actions of estradiol on the brain. PROG failed to induce consistent changes in some spontaneous motor behaviors in intact and ovariectomized rats.

Influence of the estrous cycle and estradiol on the behavioral effects of amphetamine and apomorphine in rats

This experiment was designed to investigate the influence of hormonal status of the rat on the effects of two doses of an indirect-acting dopamine agonist (amphetamine 0.25 and 1.0 mg/kg, IP) and a direct-acting dopamine agonist (apomorphine 62.5 and 250 micrograms/kg, SC) on the acquisition of conditioning avoidance responses (CARs) and the performance of some spontaneous behaviors. Active conditioned avoidance was improved by amphetamine in all the groups except in females at diestrus; apomorphine improved this response only in females at estrus and in ovariectomized rats after estradiol replacement, but the avoidance response was deteriorated in males and females at diestrus and after ovariectomy without estradiol replacement. Both dopaminergic drugs had contrasting effects on motor activity, number of rearings, and number of head shakes according to the hormonal status of the rat. Only the time spent in grooming behavior decreased after the treatment with both dopamine agonists in all of the five groups studied. These results provided behavioral evidence for the hypothesis that dopaminergic activity in the CNS is affected distinctively by modifications in the sexual hormone status (gender, estrous cycle, ovariectomy, and estradiol replacement). Relationships between ovarian hormones and dopaminergic system are discussed.

Behavioral Effects of Dopamine Agonists and Antagonists: Influence of Estrous Cycle, Ovariectomy, and Estrogen Replacement in Rats

The influence of the hormonal condition on the reactivity of central dopamine (DA) receptors was studied in male and in intact and ovariectomized (OVX) female rats. They were injected with selective DA agonists, acting either on D1 (SKF 38393, 2.5 or 10 mg/kg) or D2 receptors (PPHT, 31.3 or 125 microg/kg), or with selective DA antagonists, acting either on D1 (SCH 23390, 6.25 or 25 microg/kg), or D2 receptors (sulpiride, 10 or 40 mg/kg). The acquisition of an avoidance conditioning response (CAR) and the performance of some spontaneous motor behaviors were tested. Both D1 and D2 agonists and antagonists impaired the acquisition of CARs in diestrous, OVX, and male rats. Nevertheless, the effects of these drugs during estrus and in estradiol-primed OVX rats were different according to the drug and the dose injected. Whereas SKF 38393 failed to induce significative changes, PPHT and low doses of SCH 23390 and sulpiride improved the acquisition of CARS in those groups. The effects on conditioning were not accompanied with equivalent changes in spontaneous motor activity. Estradiol level fluctuations that occur in female rats within the estrous cycle or in OVX rats primed with estradiol would be responsive of changes in the response to DA agents. Although the reactivity of central DA systems is differentially affected by the hormonal condition of the rat, the precise mechanism of this modulatory action remains unknown.

Ketanserin Effects on Rat Behavioral Responses: Modifications by the Estrous Cycle, Ovariectomy and Estradiol Replacement

The present investigation was designed to explore the influence of estrous cycle phase, ovariectomy, and estradiol replacement on the behavioral effects of the 5-HT2 receptor antagonist, ketanserin. The parameters under investigation were ketanserin-influenced acquisition of conditioning avoidance responses (CARs), and the performance of some spontaneous motor behaviors. Ketanserin (KET 3 mg/kg) injected subcutaneously 30 min before testing improved active conditioned avoidance in intact female rats at estrus, and in ovariectomized (OVX) rats with estradiol replacement. Furthermore, KET impaired performance in female rats at diestrus and after ovariectomy. In male rats, which were included in this study in order to compare their behavioral responses with those exhibited by female rats, KET administration enhanced acquisition of CARs. These results provide behavioral evidence for the hypothesis that central serotonergic activity is a function of the hormonal status of the animal. An additional segment of the present study focussed on motoric behaviors. Spontaneous motor activity, number of rears, and time spent in grooming behavior were significantly increased by KET in all groups studied. In contrast, blockade of 5-HT2 receptors failed to induce significant changes in the number of head shakes. Relationships between ovarian hormones and the central serotonergic system are discussed.

Effects of LHRH on Avoidance Conditioning in Normally Cycling and Ovariectomized Female Rats

Several studies have demonstrated that the peptide LHRH can modify behavior in the male rat. Peripheral and intracerebral infusions of LHRH impair the acquisition of conditioned avoidance responses (CARs) and increase some spontaneous motor behaviors, such as head shaking and grooming. The present study was undertaken to detect the effects of LHRH on the acquisition of CARs and spontaneous motility in normally cycling and ovariectomized (OVX) Sprague-Dawley female rats. Normally cycling females were separated in four groups, according to the stage of the estrous cycle. Ovariectomized female rats were pretreated, 48 h before the experiment, with estradiol benzoate (10 microg/kg) or corn oil. LHRH (6.25, 25, or 50 microg/kg) was subcutaneously injected and the behavioral tests began 1 h after. Low doses of LHRH stimulated the acquisition of CARs during proestrus, estrus, and metestrus, whereas higher doses impaired conditioning in all the four stages of the cycle. High doses of LHRH impaired acquisition in OVX rats treated with oil and potentiated the depressant effects of EB on this behavior. The effects of LHRH on spontaneous motor activity were either stimulatory or inhibitory, according to the hormonal status and the dose administered. High doses of LHRH decreased motor responses in the diestrous rat. All the doses of LHRH increased the number of headshakes during proestrus, estrus, and metestrus, while the other motor responses were scarcely or not affected by LHRH in these stages. In OVX rats LHRH increased rearing, head shaking, and grooming behavior. These results support a role of LHRH in the modulation of conditioned and spontaneous behavior. They could provide an explanation to the behavioral changes observed across the estrous cycle and those observed after EB priming in OVX rats.