Chronic Treatment With Desipramine Induces an Estrous Cycle-Dependent Anxiolytic-Like Action in the Burying Behavior, But Not in the Elevated Plus-Maze Test (original) (raw)
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Interaction of desipramine with steroid hormones on experimental anxiety
Psychoneuroendocrinology, 2000
The present study analyzes if estradiol benzoate and/or progesterone interact with desmethylimipramine (DMI) to diminish experimental anxiety. The animal model of anxiety used was the conditioned defensive burying test. Dose response curves for DM1 (0.625, 1.25 and 2.5 mg/kg, every 24 h, during 21 days), estradiol benzoate (0.5, 1.0, 2.0 and 4.0 p a a t , 48 h) and progesterone (0.5, 1.0 and 2.0 m a a t , -4 h) were made in ovariectomized rats. DM1 per se decreased dose dependently the cunlulative burying time, an effect considered as anxiolytic-like. Progesterone produced a decrease in burying a t the highest dose, while estradiol benzoate had no effect on defensive burying. Both, progesterone (0.5 m u a t ) and estradiol benzoate (4.0 p a a t ) were able to decrease the cunlulative burying behavior when injected with a subthreshold dose of DM1 (1.25 m a g ) . In addition, the effect of DM1 (1.25 m a g ) plus the combination of estradiol benzoate and progesterone, sequentially administered (48 h and 4 h before the tests, respectively), also produced a synergistic decrease in burying behavior. In general, the treatments produced no changes in burying behavior latency, neither in spontaneous ambulation or in nociception. It is concluded that DM1 synergizes its anxiolytic-like effect when administered with estradiol alone or in combination with progesterone. Present data provide experimental evidence suggesting an interaction between hormones and antidepressants. Results are discussed on the basis of the interaction * Corresponding author. Tel.rSax: + 52-5-513-0432. E-n~uil uddress: fegu@neuroserver.imp-neuro.edu.mx (A. Fernandez-Guasti) 0306-45301303see front matter O 2000 Elsevier Science Ltd. All rights reserved PII: S O 3 0 6 -4 5 3 0 ( 9 9 ) 0 0 0 4 2 -6 between steroids and serotonergic or GABAergic receptors. O
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.
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
Hormones and Behavior, 2009
The development of highly selective agonists for the two major subforms of the estrogen receptor (ERa and ERϐ) has produced new experimental methodologies for delineating the distinct functional role each plays in neurobehavioral biology. It has also been suggested that these compounds might have the potential to treat estrogen influenced behavioral disorders, such as anxiety and depression. Prior work has established that the ERϐ agonist, diarylpropionitrile (DPN) is anxiolytic in gonadectomized animals of both sexes, but whether or not this effect persists in gonadally intact individuals is unknown. Isoflavone phytoestrogens, also potent but less selective ERϐ agonists, have also been shown to influence anxiety in multiple species and are becoming more readily available to humans as health supplements. Here we determined the effects of 0.5, 1 or 2 mg/kg DPN, 1 mg/ kg of the ERa agonist propyl-pyrazole-triol (PPT), 3 or 20 mg/kg of the isoflavone equol (EQ) and 3 or 20 mg/kg of the isoflavone polyphenol resveratrol (RES) on anxiety behavior in the gonadally intact male rat using the light/dark box and the elevated plus maze. We first determined that DPN can be successfully administered either orally or by subcutaneous injection, although plasma DPN levels are significantly lower if given orally. Once injected, plasma levels peak rapidly and then decline to baseline levels within 3 hours of administration. For the behavioral studies, all compounds were injected and the animals were tested within 3 hours of treatment. None of the compounds, at any of the doses, significantly altered anxiety-related behavior. Plasma testosterone levels were also not significantly altered suggesting that these compounds do not interfere with endogenous androgen levels. The results suggest that the efficacy of ERϐ agonists may depend on gonadal status. Therefore the therapeutic potential of ERϐ selective agonists to treat mood disorders may be limited.
Behavioral Neuroscience, 2008
Clinical and basic studies demonstrate that estrogen (E 2)-based therapies influence anxiety and mood, but the receptor targets (e.g. α or β isoform of the estrogen receptor, ER) for these effects requires further investigation. To address the specificity of E 2 's anxiolytic-like effects through ERβ, anxiety, motor, and nociceptive behavior of ovariectomized, wildtype (WT) and ERβ knockout (βERKO) mice was examined. Mice were administered oil vehicle or ER agonists, 17β-E 2 (E 2 ; 0.1 mg/kg; similar affinity for ERα and ERβ), and a selective estrogen receptor modulator, diarylpropionitrile (DPN; 0.1 mg/kg; greater affinity for ERβ than ERα). Performance of mice in anxiety (open field, elevated plus maze, elevated zero maze, social interaction), motor activity (activity monitor) and nociception (tailflick, pawlick) measures was compared. Results supported our hypothesis that ERβ is important in modulation of anxiety-like behavior by E 2 in some tasks. Administration of E 2 or DPN to WT, but not βERKO, mice increased open field central entries, plus maze open arm time, zero maze open quadrant time, social interaction. This pattern was neither seen in motor activity nor pain threshold measures. Thus, actions of ERβ may be important for modulating anxiety-like behavior of mice.
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.
Role of progesterone and other neuroactive steroids in anxiety disorders
Expert Review of Neurotherapeutics, 2004
Impact of anxiety disorders Gender differences & impact of female hormone fluctuations on anxiety Experimental data on the effects of female progesterone & neuroactive steroids on anxiety Impact of selective serotonin reuptake inhibitors on neuroactive steroids in anxiety disorders Expert opinion
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.
Gender Medicine, 2009
Background-With aging and menopause, which are associated with decreases in ovarian steroids such as 17β-estradiol (E 2), women might experience negative psychological symptoms, including anxiety and depression. Some women use E 2-based therapies to alleviate these symptoms, but E 2 has been associated with trophic effects that might increase vulnerability to some steroid-sensitive cancers, such as breast cancer, in both premenopausal and postmenopausal women. Objective-This study investigated the relationships between the possible beneficial effects of E 2 on anxiety and depressive behaviors concurrent with trophic effects using an animal model of E 2 decline and replacement. Methods-Dose-dependent effects of E 2 on affective, sexual, and motor behavior of young adult rats were studied. Ovariectomized (OVX) rats were administered the chemical carcinogen 7,12dimethylbenz(a) anthracene (DMBA) 1.25 mg or inactive vehicle (vegetable oil; control) by gavage. E 2 (0.03 or 0.09 mg/kg) or vehicle was administered subcutaneously 44 to 48 hours before assessments of anxiety (light-dark transition), depression (forced swim test), sexual (lordosis), and motor (activity monitor) behaviors. Fourteen weeks after carcinogen exposure, E 2 concentrations in plasma and brain regions (cortex, hippocampus, and hypothalamus) were determined. Incidences and numbers of tumors and uterine weight were analyzed. Results-Administration of E 2 (0.09 mg/kg) was associated with significant increases in antianxiety-like behavior in the light-dark transition task, antidepressant-like behavior in the forced swim test, and physiologic circulating and central E 2 concentrations compared with E 2 (0.03 mg/kg) and vehicle. Compared with vehicle, E 2 (0.9 > 0.3 mg/kg) was associated with significant increases in lordosis and uterine weight. Administration of DMBA was associated with significant increases in the incidences and numbers of tumors; this effect was augmented by E 2 administration. Conclusion-Based on the findings in this rat model, the hypothesis that E 2 may be effective in reducing anxiety and depressive behaviors and enhance sexual behavior in OVX rats, concurrent with trophic effects in the periphery, was supported. Moderate physiologic levels of E 2 might have
Neuropsychopharmacology, 2005
Variations in estradiol (E 2) may influence expression of stress-related anxiety and depression symptoms among women. Effects of E 2 and stress on anxiety and depressive behavior were investigated using an animal model. E 2 was administered subcutaneously (0, 2, 5, 10, 20, 50 mg/rat) to ovariectomized rats 2 days before testing. In experiment 1, open field (anxiety), elevated plus maze (anxiety), or forced swim test (depressive) behavior was evaluated following 20 min of restraint or no such stressor. Rats administered 5 or 10 mg E 2 , which produced physiological plasma E 2 concentrations, showed significantly less anxiety and depressive behavior and lower corticosterone levels compared to vehicle, lower, or higher E 2 dosages. Restraint stress prior to behavioral testing attenuated the antianxiety and antidepressive effects of 5 or 10 mg E 2. In experiment 2, effects of adrenalectomy or sham surgery and vehicle or corticosterone replacement in their drinking water on behavior and neuroendocrine measures of rats administered 0, 10, or 50 mg E 2 were examined. E 2 , 10 mg, compared to vehicle or 50 mg, reduced anxiety and depressive behavior of sham and adrenalectomized rats administered the low dosage of corticosterone, but not vehicle or the high dosage of corticosterone, suggesting that there may be an optimal level of corticosterone necessary for E 2 to exert these effects. Together, these data suggest that E 2 may have dose-dependent effects on anxiety and depressive behavior of female rodents, which may depend on the tone of the hypothalamic-pituitary-adrenal axis.