Response to male odours in progestin receptor- and oestrogen receptor-containing cells in female rat brain.

Sensory cues from male rats, such as odours and vaginal-cervical stimulation (VCS), play a modulatory role in female rat sexual behaviour. For example, exposure to male odours and VCS appears to be at least partially responsible for increases in sexual behaviour following repeated mating of oestradiol-primed female rats. Although there is evidence that VCS influences sexual behaviour via a ligand-independent progestin receptor (PR)-dependent mechanism, the mechanism by which odours influence sexual behaviour is not known. We tested the hypothesis that, similar to VCS, the effects of male odours on sexual behaviour are mediated by progestin receptors. Female rats were injected with the progestin antagonist, RU486, or oil vehicle and were then exposed to male-soiled bedding or clean bedding. Although exposure to male-soiled bedding resulted in higher levels of Fos immunoreactivity in brain areas associated with female sexual behaviour, the progestin antagonist did not reduce this effect. Furthermore, there was minimal coexpression of odour-induced Fos and progestin receptors in brain areas associated with female sexual behaviour. Together, these results suggest that the effects of male odours are not mediated by a PR-dependent mechanism. Therefore, we tested the hypothesis that oestrogen receptor (ER)-containing cells are involved in the effects of olfactory cues. Although there was virtually no coexpression of ERbeta and odour-induced Fos in brain areas associated with female sexual behaviour, exposure to male odours slightly increased the number of cells coexpressing ER(alpha) and odour-induced Fos in the posterodorsal medial amygdala. Although, these results do not support the hypothesis that the effects of odours are mediated by a PR-dependent mechanism, they suggest that integration of male odours and hormonal cues may occur in ER(alpha)-containing cells in the posterodorsal medial amygdala.

Sensory cues mediating mating-induced potentiation of sexual receptivity in female rats.

Repeated mating of estradiol-primed female rats increases sexual receptivity. Two studies were conducted to determine the contribution of vaginal--cervical stimulation (VCS) to this increase. In the first study, female rats were repeatedly mated for 165 min. The vaginas of half of the females were covered with tape (masked) to prevent intromissions by the males. The remaining females were unmasked. Only females receiving intromissions (unmasked) showed a significant increase in sexual receptivity during repeated mating, suggesting that VCS from intromissions is necessary for repeated mating to increase sexual receptivity. In the second experiment, female rats received either experimentally administered VCS or control scapular stimulation administered with a plastic probe 1 h prior to testing for sexual receptivity. VCS applied in this manner significantly increased sexual receptivity. Together, these findings suggest that VCS from intromissions is one of the primary factors responsible for increases in sexual receptivity following repeated mating.

Paced mating behavior in female rats in response to different hormone priming regimens.

A female rat will display a repertoire of behaviors during a sexual encounter with a male rat including sexually receptive (the lordosis response) and proceptive (hopping, darting) behaviors. In addition, when given the opportunity, a sexually receptive female rat will approach and withdraw from the male rat, controlling the timing of the receipt of mounts, intromissions, and ejaculations, a behavior known as paced mating behavior. The present experiments tested the hypotheses (1) that progesterone regulates paced mating behavior, and (2) that multiple hormone regimens used previously to induce sexual receptivity have the same effect on paced mating behavior. Paced mating behavior was assessed in sexually receptive ovariectomized female rats after treatment with: (1) estradiol benzoate (EB; 30.0 mg/kg) followed by a range of doses of progesterone (P; 1.0-8.0 mg/kg), (2) two pulses of unesterified estradiol (E2; 2.0 microg/rat) followed by 1.0 mg/rat of P, and (3) EB alone (5.0 microg/rat) for 6 days. No differences in sexual receptivity or in paced mating behavior were observed across doses of P (1.0-8.0 mg/kg). In contrast, the number of hops and darts per min increased with the dose of P administered. E2 + P administration resulted in slightly, but significantly, lower levels of sexual receptivity along with significantly longer contact-return latencies following an intromission in relation to the other treatment conditions. In addition, female rats exhibited fewer hops and darts per min in response to E2 + P than in response to EB + 8.0 mg/kg of P. The administration of EB alone for 6 days induced levels of receptivity and paced mating behavior indistinguishable from EB + P, while eliciting significantly fewer hops and darts per min than the EB + 8.0 mg/kg P treatment condition. Hormone priming regimen had no effect on the percentage of exits displayed during the paced mating tests in any experimental phase. Dose of P had no effect on paced mating behavior in sexually receptive rats. In addition, P does not appear to be necessary for the display of paced mating behavior following long-term treatment with EB. In contrast, the pulsatile administration of E2 + P induced a different pattern of paced mating behavior in sexually receptive rats.

Stanozolol, oxymetholone, and testosterone cypionate effects on the rat estrous cycle.

Anabolic-androgenic steroid (AAS) effects on the estrous cycle of adult Long-Evans rats were examined in four different experiments. Sexual receptivity, vaginal cytology, and body weight were monitored throughout two-week baseline, AAS treatment, and recovery periods. In Experiments 1-3, rats were administered stanozolol, oxymetholone, or testosterone cypionate within dose ranges selected to mimic the human abuse levels of each compound. In these studies, the highest doses of stanozolol (5 mg/kg), oxymetholone (12 mg/kg), or testosterone cypionate (7.5 mg/kg) disrupted the cyclical display of sexual receptivity and vaginal estrus. To compare effects on estrous cyclicity across AAS compounds, rats in Experiment 4 received a single dose (7.5 mg/kg) of each compound for 2 weeks. At the 7.5 mg/kg dose, all AAS compounds interfered with the cyclical display of vaginal estrus, although effects on sexual receptivity were not uniform. No striking AAS effects on body weight were seen in any experiment. The short-term administration of AAS compounds at high doses disrupts female neuroendocrine function in rats.

Inhibition of estrogen-induced sexual receptivity by androgens: role of the androgen receptor.

Both naturally occurring and synthetic androgens have been shown to inhibit estrogen-induced sexual receptivity when administered to ovariectomized (OVX) rats. The mechanisms by which androgens exert these effects, however, remain unclear. Experiments were conducted to determine the role of the androgen receptor in the inhibition of estrogen-induced sexual receptivity in OVX rats by using flutamide, an androgen receptor antagonist. In each experiment, OVX Long-Evans rats received 6 consecutive days of estradiol benzoate (EB; 2.0 microg/day) followed by 15 days of EB concurrent with flutamide (10. 0 mg/kg; twice daily) or the vehicle and one of the following androgens or the vehicle: dihydrotestosterone propionate (7.5 mg/kg), 3alpha-androstanediol (3.75 mg/kg), 17alpha-methyltestosterone (7.5 mg/kg), stanozolol (7.5 mg/kg), or nandrolone decanoate (7.5 mg/kg). On Day 15, all female rats received progesterone (P; 1.0 mg/rat) 4 h before testing. Tests for sexual receptivity were conducted on Days 3, 6, 14, and 15 of androgen/flutamide treatment. Each androgen inhibited sexual receptivity as expected, and concurrent treatment with flutamide reversed the inhibitory effects of all androgens on sexual receptivity on all test days. High levels of sexual receptivity were displayed in response to P on Day 15, regardless of experimental treatment. These results suggest that naturally occurring and synthetic androgens act at the androgen receptor to inhibit estrogen-induced sexual receptivity in OVX rats.

Stability of spatial working memory across the estrous cycle of Long-Evans rats.

In the adult rat, hippocampal dendritic synaptic connectivity in region CA1 fluctuates across the estrous cycle. This study examined the potential functional impact of such fluctuations on spatial working memory in regularly cycling Long-Evans rats. Rats were trained in a delayed non-match-to-sample radial-arm maze task and performance was monitored across the estrous cycle. There were no significant alterations in the acquisition or performance of the working memory task across the estrous cycle, with 1- or 4-h delays imposed between training and testing sessions. However, rats performed the task significantly more slowly on proestrus than on any other estrous cycle day under both delay conditions. These results indicate that while working memory remains stable, sensorimotor or motivational aspects of the performance of this radial-arm maze task may vary across the estrous cycle.

The effects of 17 alpha-methyltestosterone, methandrostenolone, and nandrolone decanoate on the rat estrous cycle.

In a series of four separate experiments, the effects of anabolic-androgenic steroid (AAS) compounds on the estrous cycle of adult Long-Evans rats were examined. Sexual receptivity, vaginal cytology, and body weight were monitored throughout a 2-week baseline, AAS treatment, and recovery periods. In Experiments 1-3, subjects were administered 17 alpha-methyltestosterone, methandrostenolone, or nandrolone decanoate at doses selected to mimic the human abuse levels of each compound. In these studies, the highest doses of 17 alpha-methyltestosterone (7.5 mg/kg) and nandrolone decanoate (5.6 mg/kg) disrupted behavioral and vaginal cyclicity, whereas the highest dose of methandrostenolone (3.75 mg/kg) appeared to have slightly less robust effects. To compare effects on estrous cyclicity across AAS compounds, subjects in Experiment 4 received a single high dose (7.5 mg/kg) of each compound for 2 weeks. At this dose, all AAS compounds interfered with vaginal cyclicity, although effects on behavioral cyclicity and uterine weight were not uniform. Across all 4 experiments, AAS effects on body weight were minimal. The short-term administration of AAS compounds at levels commonly used by humans disrupts female neuroendocrine function in a dose-dependent manner.

Anabolic-androgenic steroid effects on sexual receptivity in ovariectomized rats.

Anabolic-androgenic steroid (AAS) compounds are synthetic androgens taken by athletes to increase physical strength and endurance. Recent studies in our laboratory have demonstrated that AAS administration disrupts the estrous cycle of Long-Evans rats. The present experiments examined the effects of six commonly abused AAS compounds on sexual receptivity in ovariectomized rats. Adult female Long-Evans rats received estradiol benzoate (EB; 2.0 micrograms/day s.c.) for 6 consecutive days followed by 15 days of EB concurrent with daily s.c. injections of 7.5 mg/kg of one of the following AAS compounds: 17 alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, stanozolol, oxymetholone, testosterone cypionate, or the oil vehicle. On Day 15, all female rats received progesterone (1.0 mg/rat) 4 h before testing. Tests for sexual receptivity were conducted on Days 3, 6, 14, and 15 of AAS treatment. Although the time course of AAS effects on sexual receptivity varied, some overall effects were clear. For example, 17 alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, and stanozolol interfered with the display of sexual receptivity on Day 14, whereas oxymetholone and testosterone cypionate had no effect. Rats in all groups displayed high levels of sexual receptivity after receiving progesterone on Day 15. Our results show that AAS compounds vary in their degree of inhibition of female sexual behavior in ovariectomized rats.