Estradiol valerate elicits antidepressant-like effects in middle-aged female rats under chronic mild stress.

The purpose of this study was to analyze the antidepressant-like actions of estradiol valerate (1 or 2 mg/rat, single injection) or citalopram (5 or 10 mg/kg, chronically administered for 21 days) given independently or combined at low doses, to middle-aged ovariectomized female rats, as a model of human menopause. Animals were exposed to chronic mild stress, a model of depression that mimics anhedonia as revealed by diminished sucrose solution intake. Stressed rats decreased their sucrose preference 1 week after chronic stress and treatment with vehicle did not reverse this reduction. A single injection of estradiol valerate (2 mg/rat) produced an antidepressant-like action, evidenced as an increase in sucrose preference specific to stressed rats. Chronic citalopram (10 mg/kg) produced an antidepressant-like effect after 1 week. A single low-dose of estradiol valerate (1 mg/rat) did not potentiate or shorten the latency of action of chronic citalopram (5 mg/kg). These results reveal the antidepressant-like action of estrogens in middle-aged rats exposed to chronic stress. These data may be of importance for clinical depression in menopausal women.

Anabolic androgens restore mating after sexual satiety in male rats.

Androgen receptors and estrogen receptors importantly participate in the neuroendocrine control of masculine mating behavior. Sexual satiety is the long term inhibition of masculine mating behavior after repeated ejaculations and is associated to changes in both androgen receptor and estrogen receptor-alpha expression. Androgen receptor expression is up-regulated by systemic chronic administration of anabolic androgens, 5alpha-dihydrotestosterone or estradiol benzoate. This study was carried out to investigate the effect of these treatments on sexual satiety development and recovery; additionally flutamide or tamoxifen treatments -- alone or together with anabolic androgens -- were also included. Chronic 15-day treatment with 5alpha-dihydrotestosterone (5 mg/kg) or tamoxifen (15 mg/kg) inhibited, whereas estradiol benzoate treatment (5 mg/kg) facilitated, mating behavior during sexual satiety development. The proportion of animals that ejaculated 48 h after sexual satiety was increased after 17-day treatment with a mixture of anabolic androgens containing 2 mg/kg testosterone propionate, 2 mg/kg nandrolone decanoate and 1 mg/kg boldenone undecylenate. This effect was only blocked by the combined administration of flutamide plus tamoxifen. The data suggest that anabolic androgens metabolites synergize to restore mating behavior after sexual satiety.

Relationship between sexual satiety and brain androgen receptors.

Recently we showed that 24 h after copulation to satiety, there is a reduction in androgen receptor density (ARd) in the medial preoptic area (MPOA) and in the ventromedial hypothalamic nucleus (VMH), but not in the bed nucleus of the stria terminalis (BST). The present study was designed to analyze whether the ARd changes in these and other brain areas, such as the medial amygdala (MeA) and lateral septum, ventral part (LSV), were associated with changes in sexual behavior following sexual satiety. Males rats were sacrificed 48 h, 72 h or 7 days after sexual satiety (4 h ad libitum copulation) to determine ARd by immunocytochemistry; additionally, testosterone serum levels were measured in independent groups sacrificed at the same intervals. In another experiment, males were tested for recovery of sexual behavior 48 h, 72 h or 7 days after sexual satiety. The results showed that 48 h after sexual satiety 30% of the males displayed a single ejaculation and the remaining 70% showed a complete inhibition of sexual behavior. This reduction in sexual behavior was accompanied by an ARd decrease exclusively in the MPOA-medial part (MPOM). Seventy-two hours after sexual satiety there was a recovery of sexual activity accompanied by an increase in ARd to control levels in the MPOM and an overexpression of ARd in the LSV, BST, VMH and MeA. Serum testosterone levels were unmodified during the post-satiety period. The results are discussed on the basis of the similarities and discrepancies between ARd in specific brain areas and male sexual behavior.