Male copulatory behavior in the female rat after perinatal treatment with an antiandrogenic steroid

Adult male copulatory behavior was studied in female rats treated with an antiandrogenic steroid (cyproterone) perinatally. A time-sampling method was used to obtain a detailed record of all behavior occurring during testing. Females were treated with cyproterone either prenatally, pre- and postnatally, or not at all. They were ovariectomized and given testosterone prior to the mating tests. Treated animals engaged in significantly less female-directed activity and fewer of them engaged in copulatory acts in early tests. By the last test there were no differences between the groups. Only untreated animals ever displayed the ejaculatory pattern and only rarely.     

Facilitation of female sexual behavior in male rats by septal lesions: an interaction with estrogen.

Although destruction of the septal region markedly facilitates the lordosis behavior of female rats in response to estrogen priming, comparable lesions were found to be ineffective in facilitating the lordotic behavior of estrogen primed male rats. Neither the age at the time of septal destruction nor castration influenced the lordosis behavior of males. However, if prepubertal castrated males were given subcutaneous ovarian grafts or injected daily with 2 μgm estradiol benzoate (EB) during the 30 day period following septal destruction, a prolonged facilitation of the activational effects of EB on lordosis behavior was observed. Male rats subjected to septal destruction alone, chronic exposure to EB alone, exposure to ovarian grafts for 30 days prior to septal destruction, or chronic treatment with EB started 6 mo after septal lesioning, failed to show an increase in behavioral responsiveness to estrogen. Thus, in order for septal lesions to facilitate lordosis behavior of male rats, exposure to EB or ovarian tissue must occur within an apparent critical period following septal destruction. Adult male rats were found to be more responsive to this interaction of septal lesions and EB exposure than pubertal animals. It is suggested that the prolonged facilitation of lordosis behavior which follows septal destruction and estrogen exposure in the male rat may be due to hormonal modifications of the recovery process following brain damage.     

Lack of correlation between naloxone-induced changes in sexual behavior and serum LH in male rats

Four experiments were conducted to determine whether the action of opiate receptor antagonist drugs on sexual performance in male rats is mediated by the central release of luteinizing hormone releasing hormone (LHRH). First, in Experiment 1 it was demonstrated that administration of naloxone (20 mg/kg) caused a lengthening of postejaculatory intervals and an elevation of serum LH concentrations in gonadally intact male rats. In Experiment 2, manipulation of females' proceptive and receptive behaviors failed to reveal the reductions in ejaculation latencies and in the number of intromissions preceding ejaculation which have been previously reported after administration of naloxone to male rats. Again, the predominant response to treatment with naloxone was an increase in the length of the postejaculatory interval. In Experiment 3, pinching the tails of male rats every 30 sec after ejaculation partially abolished the relative refractory periods of the postejaculatory intervals; naloxone-induced increases in the lengths of these shortened postejaculatory intervals were nevertheless identical to those of control males, suggesting that naloxone acts to lengthen the absolute refractory period. Finally, in Experiment 4 naloxone was given to castrated males implanted with testosterone-filled silastic capsules ranging in length from 2 to 45 mm, which produced a wide range of basal serum LH concentrations. Naloxone caused an increase in postejaculatory intervals; however, this effect was not correlated with the degree to which naloxone stimulated serum LH, suggesting that the effects of naloxone on the postejaculatory interval are not mediated by a drug-induced release of LHRH.     

Differential maintenance of penile responses and copulatory behavior by gonadal hormones in castrated male rats

Sexually experienced male rats were castrated and immediately received implants of Silastic tubing containing either testosterone (T), dihydrotestosterone (DHT), estradiol (E), or nothing (blank). The ability of these hormone treatments to maintain precastration levels of copulatory behavior and ex copula penile responses was assessed for 40 days after castration. Throughout the study T- and E-treated males, but not males with DHT or blank implants, maintained normal copulatory behavior. In contrast males treated with T and DHT, but not E or blanks, maintained penile responses ex copula. In blank-treated males, penile-response latencies increased more rapidly than did intromission latencies. These results, together with those of previous studies, appear to rule out a role for estradiol and reinforce the role of androgens in the activation of rats' penile-response potential ex copula. Similarly, the results support the conclusion that in castrated male rats estradiol treatment is sufficient for the activation of masculine copulatory behavior, and that the penile actions necessary for intromission are not dependent on androgen. Thus, the evocability of penile actions and their relative androgen dependence are context sensitive.     

Disruption of male sexual behavior in rats by tetrahydrofurandiols (THF-diols)

The mitogenic agent that disrupts male and female sexual behavior has been isolated from corncob bedding. The disrupting activity resides in an isomeric mixture of linoleic acid derivatives with a tetrahydrofuran ring and two hydroxyl groups (THF-diols) that include 9, (12)-oxy-10, 13-dihydroxtstearic acid and 10, (13)-oxy-9, 12-dihydroxystearic acid. We examined the effects of exposure of male rats to THF-diols in drinking water on several parameters of male sexual behavior. THF-diols disrupt sexual behavior in male rats by reducing mounting and intromission frequencies. The mount, intromission and ejaculatory latencies are enhanced while the ejaculatory responses are diminished. These findings suggest that the THF-diols modulate hypothalamo-pituitary axis to regulate steroid hormone-dependent male sexual behavior.     

Age-related changes in sexual function and steroid-hormone receptors in the medial preoptic area of male rats

Testosterone is the main circulating steroid hormone in males, and acts to facilitate sexual behavior via both reduction to dihydrotestosterone (DHT) and aromatization to estradiol. The mPOA is a key site involved in mediating actions of androgens and estrogens in the control of masculine sexual behavior, but the respective roles of these hormones is not fully understood. As males age they show impairments in sexual function, and a decreased facilitation of behavior by steroid hormones compared to younger animals. We hypothesized that an anatomical substrate for these behavioral changes is a decline in expression and/or activation of hormone receptor-sensitive cells in the mPOA. We tested this by quantifying and comparing numbers of AR- and ERα-containing cells, and Fos as a marker of activated neurons, in the mPOA of mature (4–5 months) and aged (12–13 months) male rats, assessed one hour after copulation to one ejaculation. Numbers of AR- and ERα cells did not change with age or after sex, but the percentage of AR- and ERα-cells that co-expressed Fos were significantly up-regulated by sex, independent of age. Age effects were found for the percentage of Fos cells that co-expressed ERα (up-regulated in the central mPOA) and the percentage of Fos cells co-expressing AR in the posterior mPOA. Interestingly, serum estradiol concentrations positively correlated with intromission latency in aged but not mature animals. These data show that the aging male brain continues to have high expression and activation of both AR and ERα in the mPOA with copulation, raising the possibility that differences in relationships between hormones, behavior, and neural activation may underlie some age-related impairments.     

Age-related aspects of male rats sexual behavior with different senescence rates

Social and sexual behavior of males Wistar and senescence-accelerated OXYS rats was studied. The experimental model excluding direct interaction between partners showed that the exploratory activity decreased with aging in rats of both strains, but social motivation didn't change. No interstrain differences in intensity of sexual motivation in the presence of an inaccessible receptive female were observed in 4-month rats. The level of sexual motivation of 12-month Wistar rats didn't differ from that of 4-month animals. However, in 12-month OXYS males, sexual motivation was decreased as compared to both 4- and 12-month Wistar rats. The same regularities were found under conditions of direct interaction with a partner. Behavioral changes in 12-month OXYS rats were considered as genetically determinate abnormality at the initial stage of sexual behavior, i.e., sexual motivation. The results suggest the accelerated senescence of the reproductive system of OXYS rats.     

Male-female differences in the effects of cannabinoids on sexual behavior and gonadal hormone function

The putative role of the endocannabinoid system and the effects of cannabis use in male and female sexual functioning are summarized. The influence of cannabis intake on sexual behavior and arousability appear to be dose-dependent in both men and women, although women are far more consistent in reporting facilitatory effects. Furthermore, evidence from nonhuman species indicate somewhat more beneficial than debilitating effects of cannabinoids on female sexual proceptivity and receptivity while suggesting predominantly detrimental effects on male sexual motivation and erectile functioning. Data from human and nonhuman species converge on the ephemeral nature of THC-induced testosterone decline. However, it is clear that cannabinoid-induced inhibition of male sexual behavior is independent of concurrent declines in testosterone levels. Investigations also reveal a suppression of gonadotropin release by cannabinoids across various species. Historical milestones and promising future directions in the area of cannabinoid and sexuality research are also outlined in this review.     

Manipulation of neonatal gonadal steroid milieu and leptin secretion in later life in male and female rats

The mechanism underlying the gender-based difference in circulating leptin levels (females>males) is still uncertain, because the difference persists even after adjustment for fat mass and sex steroid concentrations. In this study, we tested the possibility that the neonatal sex steroid milieu, which is critical for the sexual differentiation of the brain, may permanently affect leptin secretion in rats of both sexes. Male rats were neonatally castrated (NC), and females were neonatally androgenized (NA) by testosterone (T). Two subsets of the NC males were given T on postnatal day 1 or 29. Appropriate controls for all these groups were prepared. The animals were sacrificed on postnatal day 57, and at this age, the percent body fat was similar among all the male and female groups. NC males had a two-fold, significantly higher level of leptin than intact males. This hyperleptinemia induced by NC was prevented by T when it was given neonatally, but not on the day 29. By contrast, NA for females was without effect on leptin titers in later life. These results suggest that neonatal T in male rats may, at least in part, mediate the sex-related difference in leptin secretion that becomes apparent in later life. However, as intact females still had significantly higher leptin titers than NC males, it is very likely that additional factors may also be responsible for the sexually dimorphic leptin secretion in rats.     

Regional brain cholecystokinin changes as a function of rough-and-tumble play behavior in adolescent rats

Brain cholecystokinin (CCK) levels have been shown to be elevated in animals defeated during adult social aggression. The present experiment evaluated whether similar effects are evident in prolonged bouts of juvenile social-play fighting, which tend to switch from largely positive to some negative affect after approximately 15 min into a half-hour play session, as indexed by a gradual shift from positively valenced 50 kHz ultrasonic vocalizations (USVs) to negatively valenced 20 kHz USVs. Given the role of CCK in both positive and negative emotional events, we examined levels of CCK-8 in tissue homogenates from 14 brain areas in animals 6h after a 30 min play bout compared to no-play control animals tested similarly in isolation for 30 min. As with patterns observed following adult defeat, significantly higher CCK levels were evident after play in the posterior neo-cortex compared to no-play control animals (+26%). Levels of CCK were also elevated in the midbrain (+35%). However, unlike in adult aggression, CCK levels were reduced in the hypothalamus (-40%) and basal forebrain (-24%) as compared to no-play animals. Posterior cortex CCK levels were positively correlated to the duration that each animal was pinned (r = +.50) which suggests that elevated CCK in the posterior cortex may be related to the negative aspects of play. Hypothalamic CCK levels were negatively related to dorsal contacts and pins (r's = -.57), and suggest that the lower CCK levels may reflect the more positive valenced aspects of play. The data indicate that CCK utilization in the brain is dynamically responsive to rough-and-tumble play.     

Aromatization and androgen stimulation of sexual behavior in male and female rats

6α-Fluorotestosterone, an androgen that is not aromatized in a standard assay system, stimulated sexual behavior in both male and female rats. In males, it was as effective as testosterone. 19-Nortestosterone also stimulated more male sexual behavior than would be expected on the basis of its aromatizability in standard assays. In other tests of the aromatization hypo we used the anti-estrogen, CI-628. This drug inhibited androgen-induced sexual receptivity in female rats, but did not inhibit androgen-induced sexual behavior in male rats. In females, CI-628 antagonized testosterone and 6α-fluorotestosterone equally. These data suggest that the structures of androgens, rather than their abilities to be aromatized, determine behavioral effectiveness.     

Sensitization of sexual behavior in ovariectomized rats by chronic estradiol treatment

The ovariectomized (OVX) rat treated with estradiol benzoate (EB) is used to elucidate neuroendocrine mechanisms of sexual behavior. Chronic behavioral and pharmacological manipulations can be confounded by rising baselines, since females are behaviorally more sensitive to repeated EB injections. The literature lacks a systematic examination of chronic effects of EB administered alone to the sexually experienced OVX rat. Long–Evans rats were repeatedly treated (8 tests) with s.c. injections of 2, 5, or 10 μg EB at different time intervals (4 or 8 days). Female sexual behaviors as well as receipt of mounts, intromissions and ejaculations from the male were observed in the unilevel 4-hole pacing chamber. The effects of adrenalectomy (ADX) and strain (Long–Evans vs. Wistar) were also assessed. Long–Evans OVX rats treated with 5 μg EB every 8 days showed persistently low levels of sexual behavior. Sensitization was most robust following 10 μg EB at 4-day intervals. Very few sexual behaviors were ever induced by 2 μg EB. ADX did not affect the development of behavioral sensitization by 10 μg EB. Therefore, to achieve a low steady state of sexual behaviors in sexually experienced Long-Evans OVX rats 5 μg of EB administered every 8 days is optimal, whereas a persistently high level of sexual behaviors is induced with 10 μg EB administered every 4 days. OVX Wistar rats are behaviorally more sensitive to EB. Behavioral sensitization to EB may serve as a mechanism to optimize reproductive success.     

Hormones and sexual behavior in relationship to aging in male rats.

To determine if the age-related decline in male sex behavior is correlated with hormonal factors, a longitudinal study was conducted. Sexually experienced males were given mating tests every 2 months from 7 through 27 months of age. To study possible relationships between changes in behavior and alterations in hormone levels, blood samples were taken before and after these bimonthly tests. At 23 months, cross-sectional studies were also conducted comparing results to those obtained in 5-month-old males. Significant changes in mating behavior first appeared at 11 months; mount latency, intromission latency, ejaculation latency, postejaculatory interval, and intercopulatory interval were increased. Similarly, detectable decreases in testosterone (T) also occurred at this age. A significant decline in luteinizing hormone (LH) was not seen until 19 months. Correlational analyses revealed small (r less than or equal to -0.29) but significant negative correlations between T and parameters of mating behavior with age. When each age was examined separately, no significant correlations appeared. Plasma T was not predictive of behavioral performance. At 23 months, cross-sectional studies revealed deficits in mounting and penile reflex behavior but ejaculatory reflex capacity was unimpaired. At 28 months, males were decapitated. Only T levels showed a significant effect of age; estradiol, prolactin, and LH were unaffected when compared to 5-month-old males. The data suggest that although there are small and significant negative correlations between circulating testosterone and parameters of mating behavior with advancing age, it is unlikely that the observed decline in testosterone is the primary cause of the age-induced behavioral deficits. It is likely that the major causal factor(s) involves non-hormone-dependent changes within the CNS.     

Variations in maternal behavior in the rat as a function of sex and gonadal state

Performance of major components of maternal care was evaluated quantitatively in several test situations for various groups of rats. Maternal behavior of concaveated ovaríectomized virgin females and castrated males was inferior on a variety of measures to that of concaveated intact virgin females. However, concaveated intact virgin females were markedly inferior to natural mothers on measures of nest building and responsiveness to an intruder. Thus, it was found that test situations other than the standard homecage test revealed previously undetected group differences and that the occurrence of pup retrieval is not a valid predictor of the performance of some major components of maternal care. In addition, it was concluded that gonadal hormones partially determine the quality of maternal responsiveness displayed by virgin females, but that gonadal hormones characteristic of the cycling female are not sufficient to increase maternal responsiveness to the level seen with natural mothers. Possible relationships between pup-induced maternal behavior and that of natural mothers are discussed.     

Early androgen treatment and male and female sexual behavior in mice

To investigate the role of neonatal androgen stimulation in the development of the potential for masculine and feminine sexual behavior in the mouse, different groups of mice were hormonally manipulated early in life. One group of female mice was administered testosterone propionate (TP) within 24 hr of birth; a second group of females was given a control injection of oil on the day of birth; a third group of females received an injection of TP on the 10th day after birth. A group of males received a control injection of oil on the day of birth. All mice were gonadectomized at about 30 days of age. At 60 days of age, mice were injected with estrogen and progesterone and tested for sexual receptivity; several weeks later all mice were injected with TP and tested for male sexual behavior. Female behavior: Females given oil at birth and females given TP on the 10th day after birth showed high levels of sexual receptivity as adults following estrogen-progesterone treatment. Females given TP on the day of birth, and male mice, rarely exhibited lordosis following estrogen-progesterone treatment. Male behavior: Most mice, regardless of genetic sex or neonatal treatment, mounted in adulthood following administration of exogenous androgen. There was little difference in mounting frequency between groups, suggesting that exogenous or endogenous androgen stimulation of the neonatal mouse does not facilitate adult mounting behavior. These data for the mouse are in essential agreement with existing data for the rat, and indicate that sexual behavioral differentiation induced by androgen stimulation in infancy is best characterized as an inhibition of the potential to display feminine sexual behavior in adulthood.     

Deterioration of male sexual behavior in rats by the new prolactin-secreting tumor 7315b

The effects of hyperprolactinemia on male copulatory behavior in adult male and female rats were studied. Hyperprolactinemia was induced by the transplantable purely prolactin-secreting tumor 7315b. Male rats were castrated and received testosterone-filled capsules of different sizes which induced normal and subnormal testosterone levels. After sexual training the rats of the experimental groups were inoculated with tumor 7315b. Three weeks after tumor-inoculation high prolactin levels (2000-30000 ng/ml) were found. During this hyperprolactinemia ejaculation latency increased significantly, while the mount frequency and intromission frequency remained unchanged. Only 9 out of 22 rats ejaculated 19 days after inoculation. Moreover, it appeared that the inhibitory effect of the tumor was as strong in the presence of normal (2.33 +/- 0.07 ng/ml) as in the presence of low (0.35 +/- 0.01 ng/ml) testosterone levels. The inhibitory effect of tumor 7315b on copulatory behavior was not influenced by adrenalectomy. In gonadectomized female rats bearing testosterone-filled capsules tumor 7315b induced prolactin levels of about 2000 ng/ml and an almost complete cessation of mounts and intromission patterns 4 weeks after tumor-inoculation. It was concluded that tumor 7315b causes a strong inhibitory effect on male copulatory behavior in male and female rats and that this effect is not influenced by the presence of normal or low testosterone levels or removal of the adrenals, suggesting a direct effect of prolactin on brain functions.     

Adult partner preference and sexual behavior of male rats affected by perinatal endocrine manipulations

Intact adult male rats, in which aromatization of testosterone to estradiol was prevented pre- and/or neonatally by ATD (1,4,6-androstatriene-3,17-dione), were repeatedly tested for partner preference behavior (choice: estrous female vs active male). In consecutive tests increasing preference scores for the female were found. Neonatal ATD males showed significantly lower preference scores for an estrous female than controls or prenatal ATD males. Prenatal ATD caused preference scores only slightly lower than those of controls. Ejaculation frequencies were markedly reduced or even absent in neonatal ATD males. Prenatal ATD treatment only had no or a moderately lowering effect on ejaculation frequency. Lordosis behavior of adult intact males was more facilitated following neonatal ATD treatment than following prenatal ATD treatment. In a number of tests the serotonergic drug 8-OH-DPAT was injected prior to testing for sexual partner preference and copulatory behavior. DPAT significantly increased preference for an estrous female in all groups of males when interaction was possible, but had no effect when sexual interaction was prevented by wire mesh. DPAT was able to increase the number of ejaculators in nonejaculating groups (i.e., perinatally ATD-treated males). "Premature ejaculations," i.e., ejaculations with the first intromission, were frequently observed with DPAT treatment in all groups of males. In conclusion, the availability of neonatal estrogen (derived from testosterone) organizes, at least partially, the preference for an estrous female normally shown by adult male rats. The lack of neonatal estrogen causes males to be less masculinized, both in partner preference behavior and ejaculatory behavior, and less defeminized in lordosis behavior.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decline of sexual behavior in castrated male rats: Effects of female precopulatory behavior

From the population of 89 adult sexually inexperienced Wistar male rats 20 animals that initiated copulatory behavior with females exhibiting low intensity of precopulatory behavior (presenting females) were preselected. Prior to castration all 20 males had the same sexual experience: three ejaculatory series in four weekly sessions with females exhibiting high intensity of precopulatory behavior (darting females). Following castration, the decline of copulatory behavior was much slower for the nine males tested with darting females as compared to the 11 males tested with presenting females. Male precopulatory behaviors (anogenital sniffing, touching flanks, etc) outlasted the loss of copulatory behavior and seem to be less dependent on both external and internal determinants. It is concluded that intensive external sexual stimuli can function to compensate, and therefore mask, the subnormal operation of androgen-dependent mechanisms in initiating the copulatory behavior.     

Hormone release during computer-monitored sexual behavior in mature and aged male rats

Sexual behavior and the increase in plasma hormone levels of LH, prolactin, and testosterone associated with sexual behavior were examined in three age groups of sexually naive male rats. The two younger groups (5- and 11-month-old) mated normally and their behavioral latencies decreased significantly following sexual experience. Both plasma testosterone and LH concentrations increased significantly following entrance of a receptive female into the mating arena. Plasma prolactin levels rose but not significantly. However, the 27-month-old rats neither mated nor showed an increase in the three plasma hormone concentrations during exposure to a receptive female. Only basal testosterone levels were significantly lower than those of the younger animals. Low testosterone levels possibly contributed to deficiencies in both behavior and its associated hormone release. The monitoring of sexual behavior was facilitated by a computer, programmed to record, store, and analyze behavioral events.