Sexual Behavior In Adult Rats Research Articles

Double perinatal stress reduces the sexual response of adult female Wistar rats.

Early-life stress affects physiological development and produces changes in various aspects of emotional behavior. We sought to examine the effects of double perinatal stress (DPS)-a combination of prenatal systemic hypoxic-ischemic (HI) insults and repeated early maternal separation-on the estrus cycle and sexual behavior of adult rats. HI was induced by clamping the uterine arteries of pregnant rats for 45minutes on the 18th day of gestation (HI group). Sham control animals received laparotomy and anesthesia only. Pups were born at term. Maternal separation was performed from postnatal day 1 (P1) (P0 = day of birth) to P15. At P90, the sexual response of females in estrus was evaluated. Statistical analysis was performed using 2-way analysis of variance followed by Tukey's test. We considered the estrous cycle and sexual behavior of female rats submitted to DPS, as well as the influence of female behavior on the sexual response of male rats. Rats submitted to DPS showed a reduction in the lordosis quotient and in the lordosis rate, suggesting a reduction in female sexual receptivity. DPS female rats showed a reduction in the number of hops and darts and in the genital exploration time rate, suggesting a reduction in sexual proceptivity. In addition, males that interacted with DPS females showed a reduction in the number of ejaculations and in copulatory efficiency. Developing a deeper understanding of perinatal factors that affect adult female sexual response will allow for more effective interventions to prevent and treat such changes. On the other hand, the analysis of the sexual response allows assessing the quality of life and the general state of health. The development of animal models to investigate the environmental factors that interfere in the female sexual response may allow researchers to propose and test new therapeutic strategies. On the other hand, care must be exercised when interpreting animal data and extrapolating these results to estimate the possible effects of perinatal stressors on the human sexual response. Our results revealed that females subjected to DPS showed long-term effects on sexual behavior. In conclusion, managing stressors in prenatal life and early postnatal life can prevent problems in adult sexual life and improve overall health.

Effects of ivermectin treatment during prepubertal and pubertal period on sexual parameters and sexual behavior in adulthood in rats

Pediculosis is a parasitic disease that is considered a serious global public health problem. It is caused by the ectoparasite that is popularly known as lice, mainly affecting children in early childhood. The most commonly used treatment to combat this parasitosis is the macrocyclic lactone ivermectin (IVM). However, the use of IVM is contraindicated in children who are younger than 5 years old or who weigh <15 kg because some types of drugs that are used during certain periods of brain maturation can lead to behavioral disorders. The present study evaluated the effects of IVM treatment during the prepubertal and pubertal period on sexual behavior in adulthood in male rats. Genital grooming, preputial separation, sexual behavior, sexual motivation, relative organ weight, the gonadosomatic index, and histopathology were evaluated. Oral dose of 0.2 mg/kg (therapeutic dose) of a commercial IVM formulation was administered. IVM affected genital grooming but did not influence preputial separation in prepubertal rats. Prepubertal IVM administration did not impair sexual behavior in adult rats, with the exception of the time of residence with female rats in the sexual motivation test. It did not affect relative organ weights, with the exception of the relative weight of the full seminal vesicle. It did not alter the gonadosomatic index, and no histopathological alterations were observed in different organs. These results indicate that administration of a therapeutic dose of IVM during the prepubertal and pubertal period does not alter parameters of sexual development or sexual behavior in adult male rats.

Pubertal pair‐housing facilitates adult sexual behavior in male rats

This study examined the effects of pubertal testosterone (T) and social housing manipulations on male sexual behavior in adult rats. Prepubertal rats were castrated at 21 days of age (P21) and implanted with either blank or T-releasing pellets. At the onset of puberty, P28, half the rats in each treatment group were either single- or pair-housed with a male of the same hormone condition through P56, at which time pellets were removed and all rats were single-housed. In adulthood (P84), all rats received T replacement and were tested for sexual behavior. Rats pair-housed during adolescence showed more sexual behavior and greater improvement of sexual performance over repeated tests than single-housed rats, regardless of pubertal T status. Pubertal T, however, did facilitate the frequency of anogenital investigation. Thus, in male rats, social interactions during adolescence are more important than exposure to pubertal T in enhancing adult sexual behavior.

Effects of neonatal handling on social memory, social interaction, and number of oxytocin and vasopressin neurons in rats

Early-life environmental events can induce profound long-lasting changes in several behavioral and neuroendocrine systems. The neonatal handling procedure, which involves repeated brief maternal separations followed by experimental manipulations, reduces stress responses and sexual behavior in adult rats. The purpose of this study was to analyze the effects of neonatal handling on social behaviors of male and female rats in adulthood, as manifest by the results of social memory and social interaction tests. The number of oxytocin (OT) and vasopressin (VP) neurons in the paraventricular (PVN) and supraoptic (SON) nuclei of hypothalamus were also analyzed. The results did not demonstrate impairment of social memory. Notwithstanding, handling did reduce social investigative interaction and increase aggressive behavior in males, but did not do so in females. Furthermore, in both males and females, handling was linked with reduced number of OT-neurons in the parvocellular region of the PVN, while no differences were detected in the magnocellular PVN or the SON. On the other hand, handled males exhibited increased number of VP-neurons in the magnocellular zone of the PVN. We may conclude that the repeated brief maternal separations can reduce affiliative social behavior in adult male rats. Moreover, the disruption of the mother–infant relationship caused by the handling procedure induced long-lasting morphological changes in critical neuroendocrine areas that are involved in social bonding in mammals.

Evidence that the deficit in sexual behavior in adult rats neonatally exposed to citalopram is a consequence of 5-HT 1 receptor stimulation during development

Neonatal (postnatal days 8–21) exposure of rats to the selective serotonin reuptake inhibitor (SSRI), citalopram, results in persistent changes in behavior including decreased sexual activity in adult animals. We hypothesized that this effect was a consequence of abnormal stimulation of 5-HT 1A and/or 5-HT 1B receptors as a result of increased synaptic availability of serotonin during a critical period of development. We examined whether neonatal exposure to a 5-HT 1A (8OH-DPAT) or a 5-HT 1B (CGS 12066B) receptor agonist can mimic the effect of neonatal exposure to citalopram on adult sexual behavior. Results showed that neonatal treatment with 5-HT 1B receptor agonist robustly impaired sexual behavior similar to the effect of citalopram, whereas exposure to 5-HT 1A receptor agonist only moderately influenced male sexual activity in adult animals. These data support the hypothesis that stimulation of serotonin autoreceptors during development contributes to the adult sexual deficit in rats neonatally exposed to citalopram.

Neonatal citalopram exposure produces lasting changes in behavior which are reversed by adult imipramine treatment

Neonatal exposure to antidepressants, including selective serotonin reuptake inhibitors such as citalopram, induces behavioral disturbances which persist in mature rats. These disturbances have been proposed to model the symptoms of endogenous depression. However, to date there is scant evidence for the predictive validity of any of these behaviors in response to adult antidepressant treatments. In order to directly assess the predictive validity of the early antidepressant exposure paradigm, the present study examined whether the behavioral abnormalities observed in adult animals exposed as neonates to citalopram can be reversed by adult antidepressant treatment with the prototypic antidepressant, imipramine. As noted earlier, neonatal citalopram exposure robustly increased locomotor activity and impaired male sexual behavior in adult rats. These behavioral changes were reversed following chronic adult imipramine treatment. No such reversal was observed in handled, saline treated rats. The present data support the hypothesis that some of the lasting behavioral abnormalities induced by early antidepressant exposure are sensitive to clinically relevant antidepressant treatments thus adding a measure of predictive validity to this paradigm as a model of these depressive symptoms.

Estrogen-Induced Abnormal Morphology of the Penis, Altered Sexual Behavior and Loss of Fertility in Male Rats

Penile abnormalities, including hypospadias and/or smaller phallus, have been reported in laboratory animals and alligators exposed to estrogenic chemicals, as well as in offspring of women treated with diethylstilbestrol (DES) during pregnancy. In addition, estrogen receptors have been identified in the penis; however, the mechanism of estrogen action in inducing penile abnormalities is not clear. In this study we determined whether reduced fertility and altered sexual behavior in adult rats treated with (DES) neonatally or at adulthood are associated with structural changes in the penis and whether testosterone (T) supplementation can reverse the effects of DES. Plasma T was significantly decreased (P < 0.05), whether DES was given neonatally or at adulthood. The penile morphology was adversely affected in rats that received DES neonatally, including reductions in length, diameter and weight of the penis, and complete replacement of cavernous spaces with fat cells in the body of the penis. None of the neonatal DES-treated males (0/6) sired a pup or produced a copulatory plug, in contrast to 6/7 in controls. Supplementation with T restored penile morphology and sexual behavior (as indicated by the presence of copulatory plugs, 6/6) to an almost normal level, but fecundity (ability to sire pups, 3/6) only partially. Conversely, penile morphology was not altered in rats that received DES at adulthood, although adverse effects on sexual behavior and fecundity, and their prevention by T supplementation, were similar to those of the neonatal group. Hence, neonatal estrogen exposure, but not adult estrogen exposure, leads to abnormal morphology of the penis; however, both exposures result in reduced fertility and altered sexual behavior. Supplementation with T prevents many estrogen-induced effects.

Impact of single neonatal serotonin treatment (hormonal imprinting) on the brain serotonin content and sexual behavior of adult rats

Hormonal imprinting takes place perinatally at the first encounter between the developing receptor and its target hormone. As a consequence of imprinting the receptor accomplishes its maturation and reaches the binding capacity characteristic to the adult age. In the excess of target hormone or presence of molecules similar to the target hormone, which are able to bind to the unmatured receptors, faulty imprinting develops with life-long consequences. At present, serotonin was given to neonatal rats and their sexual activity, brain serotonin level and steroid receptor's binding capacity was measured in adult age. Brain serotonin level was significantly reduced in male's striatum and parallel with this, male's sexual activity significantly increased. In other regions of the male brain (prefrontal cortex, hypothalamus, hippocampus) there was a statistically non-significant tendency for a decrease in serotonin level. No significant differences were detected in female brain values, and there was only slight change in female's sexual activity. There was also no change in the binding capacity of thymic glucocorticoid and uterine estrogen receptors. The experiments call attention to the possibility of perinatal imprinting by a neurotransmitter causing changes in brain neurotransmitter level for life, which is manifested in altered sexual activity.

Effect of single neonatal treatment with the soy bean phytosteroid, genistein on the sexual behavior of adult rats.

Hormonal imprinting develops during the perinatal critical period, when the target hormone meets the yet unmatured receptor. As a consequence of imprinting the receptor accomplishes its maturation reaching the binding capacity characteristic to adults. In this period in the presence of foreign molecules similar to the target hormone faulty imprinting may occur with life-long consequences. Soy bean contains phytosteroids which can mimic estrogen effects. In the present experiments single genistein (20 microg) or combined genistein + benzpyrene (20 microg) treatments were done neonatally and the sexual behavior of male and female adult animals was studied. Genistein significantly increased the lordosis quotient of females, which was compensated by neonatal benzpyrene treatment. Genistein also enhanced the sexual activity of males, and this was significantly not reduced by parallel benzpyrene treatment. The results show that neonatal genistein exposure can imprint sexual activity for life and the presence of a second imprinter can modify genistein's behavioral effect.

The effect of a single neonatal treatment (hormonal imprinting) with the antihormones, tamoxifen and mifepristone on the sexual behavior of adult rats

Hormonal imprinting takes place perinatally during the first encounter between the hormone and its developing receptor. The presence of an excess of related molecules in that time provokes faulty (pathological) imprinting. In the present experiments single-neonatal treatment with 100 μ g of tamoxifen completely abolished the adult male and female rats’ sexual activity. Similar treatment with 100 μ g of mifepristone (RU486) significantly enhanced the males sexual activity and non-significantly increased that of the females. The results demonstrate the importance of pathological imprinting during the perinatal development of sexual behavior. There are clear differences between the molecules having steroid (mifepristone) or non-steroid (tamoxifen) character, mediated through a ligand–receptor complex, and its effect in activating particular genes.

Effect of neonatal administration of an antidopaminergic drug (metoclopramide) on sexual behavior of male rats.

Metoclopramide is an antidopaminergic drug that binds D2 receptor at the central nervous system and peripheral levels. Recent studies have demonstrated the presence of a sexually dimorphic nucleus in the anterior hypothalamus of rats and humans. The sexual differentiation of brain and its expression on sexual behavior is directed by catecholamines and steroids, which in turn will determine the masculinization of the preoptic area of the hypothalamus. Metoclopramide blocking dopaminergic receptor inhibits dopamine action and therefore brain masculinization. To determine the effects of the administration of this antidopaminergic drug in neonatal male rats, the design of the study considered measurements of mounts, penis intromission, and ejaculation in adult male rats treated neonatally with 100 microg metoclopramide. The administration of the drug or the vehicle (control) was by subcutaneous route during the third and fifth days of postnatal life. Six of 10 neonatally treated rats did not express male sexual activity in adulthood, while all control rats showed the characteristic pattern of male sexual behavior. Frequency of ejaculation in the rats treated with metoclopramide was 1.5 +/- 1 as compared to 5.0 +/- 0.9 in control rats (p < .01). There were meaningful differences with respect to the frequency of intromission in experimental rats (16 +/- 8) compared to control rats (115 +/- 18; p < .01). There is strong evidence that metoclopramide neonatally administered inhibits male sexual behavior in adult rats. Dopamine may be implicated in the process of neonatal brain sexual differentiation.

Effect of Fetal Digoxin Exposure (Imprinting) on the Sexual Behavior of Adult Rats

1. Digoxin exposure of rat fetuses at the 15th, 17th and 19th day of pregnancy by treating the mother (with 9 μg digoxin altogether) caused alterations in the sexual behavior of adult rats (3-month-old males and six-month-old ovariectomized and hormone-treated females). 2. The number of active males was significantly higher in the treated group and ejaculation as well as multiple ejaculation occurred only here. Females also were more receptable after fetal digoxin treatment. It is known from the literature that long-term digoxin treatment in adult age influences (reduces) the male sexual activity in humans. In the rat, the opposite effect was observed after fetal treatment. 3. The experiments call attention to the prolonged effect of fetal digoxin exposure caused by the treatment of the mother.

Effect of perinatal vitamin A or retinoic acid treatment (hormonal imprinting) on the sexual behavior of adult rats.

Single neonatal treatment with vitamin A (retinol) dramatically reduced the sexual activity of adult male rats. In females there was a significant decrease in the Meyerson index and a non significant decrease in the lordosis quotient. The effect of three perinatal treatments (at the first, third and fifth day) with all-trans retinoic acid was much weaker, causing only a significant increase in the time of the first ejaculation in males and non-significant decrease in the lordosis quotient of females. The experiments call attention to the false imprinting provoking effect of materials acting on members of the steroid receptor superfamily with possible human health aspect.