Sexual differences in the neonatal serotonin effect on hormone secretion in rats

A number of authors in the literature have reported facilitatory or inhibitory effects of serotonin (5-HT) on gonadotropin secretion, sexual hormones content or sexual behavior, but little information has been reported about the possible role of serotonin administered during the critical period of sexual differentiation. To test this possibility, we have injected a 5-HT intraventricularly to neonate male and female rats in order to examine the influence during the critical period of this single treatment on the adult sexual hormone content and sexual behavior. Neonatal administration of 5-HT in the brain decreases significantly estradiol content of adult females, without affecting testosterone level in males. Neither male nor female sexual behavior was affected by 5-HT injection on day 1 of life. These data evidence a sexual difference of serotonin administration during the critical period on gonadal hormones secretion in adulthood.     

Sexual experience of male rats influences anxiety-like behavior and androgen levels

There is a wide body of literature to suggest that sexual experience may influence androgen secretion in various species, in turn, androgens may also influence anxiety. We hypothesized that sexual experience may alter anxiety behavior and secretion of endogenous androgens. Experiment 1: anxiety behavior of rats with a history of sexual experience was compared to that of sexually-inexperienced, na?ve male rats. Sexually-experienced rats showed less anxiety-like behavior in the open field and elevated plus maze, and exhibited increased plasma and hippocampal testosterone (T) levels. Experiment 2: the effects of recent sexual experience on anxiety behavior of sexually-experienced male rats, sexually-responsive but inexperienced male rats, and sexually-unresponsive, inexperienced male rats exposed to a receptive female immediately prior to testing was examined. Recent sexual experience significantly decreased anxiety-like behavior in the open field, elevated plus maze, and the elevated zero maze tasks, and tended to decrease anxiety-like behavior in the light-dark task. Rats with recent sexual experience exhibited increased plasma and hippocampal T levels. Experiment 3: to examine the effect of recent sexual experience, anxiety behavior of rats with a history of sexual experience that received sexual experience with a stimulus female immediately prior to testing was compared to that of rats with a history of sexual experience that did not receive sexual experience immediately prior to behavioral testing. Experienced rats that were exposed to a female prior to testing showed decreased anxiety-like behavior in the open field, elevated plus maze, and light-dark transition tasks, and showed increased plasma and hypothalamic, T and 3alpha-diol, and increased hippocampal T. Thus, sexual experience is associated with lower levels of anxiety-like behavior and higher levels of androgen secretion.     

Use of peripheral blood transcriptome biomarkers for epilepsy prediction

Fenfluramine reduces hunger and promotes body weight loss by increasing central serotonin (5-HT) signaling. More recently, neuropeptides have been linked to the regulation of feeding behavior, metabolism and body weight. To examine possible interactions between 5-HT and neuropeptides in appetite control, fenfluramine (200 nmol/0.5 μl/side) was administered directly into the hypothalamic paraventricular nuclei (PVN) of male rats. Bilateral fenfluramine produced significant hypophagia and increased expression of PVN corticotropin releasing factor (CRF) mRNA and neuropeptide Y (NPY) mRNA in the arcuate nucleus within the first hour after drug administration. Fenfluramine's effects on feeding behavior and mRNA expression were blocked by PVN injections of a 5-HT(1-2) receptor antagonist, metergoline (15 nmol/0.5 μl/side). These data suggest that 5-HT neurons targeting hypothalamic paraventricular CRF neurons may participate in an appetite control circuit for reducing food intake.     

Selective effects of beta-endorphin infused into the hypothalamus, preoptic area and bed nucleus of the stria terminalis on the sexual and ingestive behaviour of male rats

beta-Endorphin was infused bilaterally into the medial preoptic area-anterior hypothalamic continuum at doses of 5, 10 and 40 pmol each side. The highest dose selectively abolished mounting, intromitting and ejaculating in sexually experienced male rats paired with an oestrous female. Males infused with 40 pmol beta-endorphin still followed the female, investigated her anogenital region and other parts of her body, but made abortive attempts to mount. A dose of 5 pmol beta-endorphin had no effect, but 10 pmol proved partially effective. The same males, in other tests, were allowed to ingest a highly preferred, sweet, non-calorific solution (acesulfame-K) in the absence of a female. beta-Endorphin infusions (up to 40 pmol) into the same area of the hypothalamus had no effect on this behaviour. Control males allowed simultaneous access both to an oestrous female and to the sweet solution copulated normally but reduced their ingestive behaviour, despite there being sufficient time during tests for both to occur. beta-Endorphin (40 pmol) infused into the preoptic area-anterior hypothalamic continuum under these conditions suppressed sexual interaction, but ingestion of acesulfame-K increased to values observed when the female was absent. beta-Endorphin infused into neighbouring areas of the brain had different behavioural effects. Sexual behaviour was not inhibited, and ingestion of acesulfame-K was unaltered, when beta-endorphin was infused either into the bed nucleus of the stria terminalis or the rostral ventromedial hypothalamus. However, infusions of cholecystokinin-8 into the ventromedial hypothalamus suppressed acesulfame-K ingestion in most animals, showing that the cannulae were placed in an area regulating ingestive behaviour. The inhibition of sexual behaviour after preoptic area-anterior hypothalamic continuum infusions of beta-endorphin was prevented by either pretreating rats with 1 mg/kg naloxone intraperitoneally, or by infusing a putative delta opiate receptor blocker (0.5 pmols ICI 174864) into the preoptic area-anterior hypothalamic continuum 5 min prior to beta-endorphin treatment. ICI 174864 administered alone significantly increased mount rate and reduced the post-ejaculatory refractory period in copulating males. These experiments suggest that there is both neurochemical and neuroanatomical specificity relating beta-endorphin to sexual behaviour in the male rat.     

A possible role for angiotensin II in the regulation of male sexual behavior in rats

To investigate the possibility that angiotensin II (AII) is involved in the regulation of male sexual behavior, AII was injected intraventricularly into sexually experienced male rats immediately prior to mating tests. Third ventricular administration of 0.48 nmol AII resulted in an increased latency to the initiation of copulatory behavior (625% of control values), and administration of 4.8 nmol had a similar effect on initiation latencies (650% of control values) and, additionally, significantly increased the number of intromissions preceding ejaculation (the ejaculatory threshold, to 130% of control values) and the interval to reinitiate copulatory behavior after ejaculation (the postejaculatory interval, to 125% of control values). Water intake was affected only by the higher dose of AII, with no animals drinking in the 15 minutes following saline or 0.48 nmol AII and 69% of the rats treated with 4.8 nmol AII drinking (mean intake 1.5 +/- 0.26 ml for those rats drinking). These data demonstrate that AII can suppress male sexual behavior, and that this suppression is not due simply to a stimulation of drinking.     

L-精氨酸甲基酯对大鼠垂体-睾丸轴激素分泌的剂量影响

目的　探讨L 精氨酸甲基酯 (N nitro L argininemythelester,L NAME)剂量与血清内促性腺激素和睾酮含量的关系 ,阐明一氧化氮 (Nitricoxide,NO)对垂体 睾丸轴内分泌功能的调节作用。方法　健康成年雄性SD大鼠分为 8组 ,每组 5只 ,腹腔内给予不同剂量的L NAME(0～ 70mg/kg) ,对照组注射D NAME放射免疫法测定血清中促卵泡素 (Folliclestimulatinghormone,FSH)、促黄体素 (Luteinizinghormone ,LH)、雄激素含量 ,对所得数据用SPSS软件包进行统计学处理。结果　L NAME剂量越大 ,FSH含量越低 (r =0 947,p <0 0 1) ,LH含量也随剂量的增加而降低 (r=0 983 ,p <0 0 1) ,而雄激素浓度则随剂量的增加而增加(r=0 993 ,p <0 0 1)。 结论　L NAME剂量与促性腺激素和睾酮分泌具有高度相关性     

Medial preoptic-anterior hypothalamic lesions in prepubertal male cats: effects on juvenile and adult sociosexual behaviors

Bilateral lesions of the medial preoptic-anterior hypothalamic (MP-AH) area were made in prepubertal male cats at 6-8 weeks of age. All subjects were subsequently reared in groups containing male and female peers, until the last phase of the juvenile period when an adult estrous female was inserted in these social groups. In spite of such optimal conditions for the practice of sociosexual behaviors during development, no sparing of adult male copulatory behavior was observed in these MP-AH animals during testing in adulthood. This finding, while consistent with earlier work on dogs, contrasts with the results obtained in prepubertally lesioned rats. Urine spraying, another sexually dimorphic behavior which is eliminated by MP-AH lesions in adult cats, was spared by prepubertal lesion placement. Heterotypical sexual behavior was not enhanced by prepubertal MP-AH lesion placement, as it is with postpubertal placement. In the present study, therefore, different behavioral systems influenced by the MP-AH area showed varying degrees of plasticity. As found in dogs, prepubertal MP-AH lesions enhanced and accelerated testosterone secretion in cats.     

Activation of sexual reflexes of male rats by dihydrotestosterone but not estrogen

Previous studies have shown that withdrawal and administration of testosterone propionate (TP) has a quantitative influence on sexual reflexes which parallels changes in copulatory activity following castration and administration of TP. The present study involving castrated spinal male rats explored further this parallel, focusing on the effects on sexual reflexes of the administration of dihydrotestosterone propionate (DHTP) and estradiol benzoate (EB), both of which can activate sexual behavior in spinally intact castrated male rats, but only if given in very large doses for a prolonged period of time. A parallel effect on reflexes and behavior was not found inasmuch as DHTP activated sexual reflexes at a dose (200 microgram daily) considerably below that needed to activate behavior, and EB did not appreciably activate reflexes, even after prolonged treatment at levels (100-200 microgram) higher than necessary to activate behavior. The results, with EB in particular, point out that the display of intromissive and ejaculatory patterns in rats may not involve spinal neural mechanisms that are customarily associated with these behavioral patterns.     

Are all males equal? Anatomic and functional basis for sexual orientation in males.

In non-human primates anterior hypothalamic nuclei are closely involved in heterosexual activity in males. In humans, hypothalamic nuclei which correspond to these nuclei in non-human primates have been shown to have a neuronal density in homosexual men that is approximately half of that seen in heterosexual men. In addition, homosexual men exhibit a positive luteinizing hormone response to acutely administered estrogen that is intermediate between women (flat response) and heterosexual men (exaggerated response). Furthermore, on the basis of serum testosterone concentrations in similarly feminized transsexual males on estrogen/progestogen treatment 3 distinct groups can be identified. It is postulated that anatomic differences in the anterior hypothalamic nuclei that regulate sexual orientation in males may lead to alteration in the gonadotropin releasing hormone (GnRH) pulse/frequency leading to a more female-type pattern of gonadotropin secretion in homosexual males. Based on data in transsexual males this pattern may be more or less of the female-type in subsets of male homosexuals.     

Hypothalamic nuclear progestin receptors and the duration of sexual receptivity in ovariectomized and ovariectomized-hysterectomized rats

In order to determine if the enhancement of sexual behavior in hysterectomized rats is associated with an increased level of hypothalamic nuclear progestin receptors, ovariectomized (OVX) and ovariectomized-hysterectomized (OVHX) rats were injected with 2 micrograms estradiol benzoate. Twenty-four hr later, animals were injected with 0.5 mg progesterone and were tested for sexual receptivity every 4 hr. Hysterectomy had an overall facilitatory effect on lordosis and increased the duration of the period of sexual receptivity by about 4 hr. In a second experiment, similarly-treated animals were killed 4, 8, or 12 hr after progesterone injection, and hypothalamic nuclear progestin receptor levels were measured. In contrast to what has been reported for guinea pigs, nuclear progestin receptor levels decreased to baseline 8-12 hr before the termination of sexual receptivity. Nuclear progestin receptor concentrations were higher in OVHX rats than in OVX rats at 4 hr after progesterone injection, and there was a trend toward higher receptor concentrations in OVHX rats at 8 hr. These results demonstrate that hysterectomy-induced facilitation of sexual receptivity is associated with an increased level of hypothalamic nuclear progestin receptors. Furthermore, they suggest a fundamental difference in the regulation of nuclear progestin receptor retention between rats and guinea pigs.     

Effect of lesion location within the medial preoptic-anterior hypothalamic continuum on maternal and male sexual behaviors in female rats

Lesions of the medial preoptic-anterior hypothalamic continuum (MPOA-AH) are known to disrupt both maternal behavior and male sexual behavior in the rat. In order to test the hypothesis that the two behaviors involve different neural systems in the MPOA-AH, small bilateral lesions were made in different anterior-posterior locations in the MPOA-AH of maternal-sensitized, testosterone-treated female rats, and the effects of these lesions on maternal and male sexual behaviors were assessed. Lesions centering in the MPOA disrupted maternal behavior (pup retrieval, nest building, and nursing), with anterior MPOA lesions being more effective (on pup retrieval and nest building) than posterior MPOA lesions. Lesions centering in the AH had little or no effect on maternal behavior. By contrast, male sexual behavior (mounting) was strongly disrupted by lesions in either the MPOA or the AH, with lesions in the rostral AH being most effective.     

Level searching: a new assay of sexual motivation in the male rat

Mendelson and Gorzalka recently described a bilevel chamber for the evaluation of rodent sexual behavior. In initial studies it was observed that during 5 min adaptation periods prior to the introduction of a sexually receptive female rat, male rats with prior sexual experience in these chambers would move from level to level in apparent search for the female rat. In Experiment 1, we examined the acquisition of this level searching behavior in male rats. Sexually active male rats were given access to either sexually receptive or nonreceptive female rats following a 5 min period alone in the bilevel chamber. Only male rats that pursued and copulated to ejaculation with sexually receptive females in the bilevel chamber significantly increased the number of their level to level movements in subsequent tests during the 5 min periods prior to the introduction of the female rat. In Experiment 2, male rats that had acquired asymptotic rates of level searching showed a significant attenuation of this behavior when the presentation of a female rat into the chamber was discontinued. These findings lead us to conclude that the increase in level to level movement by the male rat represents a sexually motivated search for the female rat. We suggest that the analysis of the acquisition, maintenance, and extinction of level searching behavior might serve as a simple assay of sexual motivation in the male rat.     

Neonatal catecholaminergic influence on behaviour and sexual hormones.

There is evidence of a sexually dimorphic effect of serotonin administration during the critical period of sexual differentiation on gonadal hormone secretion in adulthood. To investigate the possible involvement of catecholamines on these mechanisms, we have injected dopamine or noradrenaline intraventricularly into neonatal male and female rats to examine the influence, during the critical period, of this single treatment on the adulthood. Gonadal sex hormone contents, sexually dimorphic behaviours, and catecholaminergic distribution in hypothalamic and extrahypothalamic areas were studied. Both catecholaminergic treatments in females resulted in a reduced striatal dopaminergic activity and an increase in the hypothalamic noradrenergic ratio, while a reduction in the open field activity occurred in the same groups. These results suggest the possible involvement of striatal dopamine and hypothalamic noradrenaline in the differentiation of exploratory activity in females. A reduction in copulatory behaviour was shown in adults of both sexes after neonatal dopaminergic administration, but gonadal hormone levels were not affected in the same way. This indicates the existence of different facets of sexual differentiation, with striatal dopamine and hypothalamic noradrenaline playing important roles in neurobehavioural differentiation.     

Effects of undernourishment on the hypothalamic orexinergic system

The present study examined the effects of a severely restricted diet during the pre- and postnatal periods with later nutritional rehabilitation on orexin hypothalamic neurons in male and female Wistar rats.Immunocytochemistry was used to reveal orexin-immunoreactive (orexin-ir) cells in the ventromedial hypothalamus (VMH), dorsomedial hypothalamus (DMH), lateral hypothalamic area (LH) and the perifornical nucleus (PF).Dietary restriction decreased the number of orexin-ir cells in the LH, whereas DMH or PF orexin-ir populations were not affected in either male or female rats. Nutritional rehabilitation resulted in a differential recovery that depended on the period during which rehabilitation occurred and on the sex of the animal. In summary, our study suggests that the hypothalamic nuclei implicated in eating behavior present a differential vulnerability to adverse environmental conditions during development. Specifically, among the studied nuclei only the LH orexin-ir cells were sensitive to severe food deprivation during development in male and female rats. These results suggest that starvation interferes with developmental events that occur during CNS sexual differentiation.     

Naloxone blocks place preference conditioning after paced mating in female rats

Sexual behavior in male rats induces a positive affect as evaluated by conditioned place preference (CPP). In addition, when females control or "pace" the rate of sexual interaction, a clear CPP is also observed. The reward state induced by mating in male rats is blocked by the injection of the opioid antagonist naloxone. In the present experiment, a dose of 4 mg/kg of naloxone completely blocked the CPP induced in females by paced mating. It appears that a common opioid system is involved in the positive affect induced by sexual behavior in both male and female rats.     

Microinjection of different doses of corticotropin-releasing factor into the medial prefrontal cortex produces effects opposing anxiety-related behavior in rats

Corticotropin-releasing factor (CRF) in the medial prefrontal cortex (mPFC) is suggested to play an important role in mediating fear, anxiety, and depression. The results of the studies of the actions of CRF in the mPFC regarding anxiety-related behavior, however, seem contradictory. In one study, microinjection of CRF into the mPFC produced an increase in anxiety-related behavior on the elevated plus maze, whereas in another study CRF produced an anxiolytic-like effect. To test whether the different doses of CRF used in these experiments are responsible for the differing results, we examined the dose-dependent effects of CRF (0.015, 0.05, 0.15, 0.5, and 1.0 μg/0.5 μL/site) microinjected into the bilateral mPFC of male Wistar rats on anxiety-related behavior in the elevated plus maze. We found that microinjection of 0.05 μg CRF significantly decreased the number of open-arm entries, whereas 1.0 μg CRF significantly increased the time spent on the open arms. The results indicate that CRF has effects opposing anxiety-related behavior in the elevated plus maze: anxiety-related behavior at a lower dose and an anxiolytic-like effect at a higher dose.     

Sexual behavior of male rats is differentially affected by timing of perinatal ACTH administration.

The laboratory rat was used as a model to investigate the effect of pre- and/or postnatal ACTH administration on sexual differentiation of the brain. Pregnant Sprague-Dawley rats were injected with ACTH 1-24 (10 micrograms/kg/2x/day or 500 micrograms/kg/2x/day); postnatally treated neonates were injected with the above dosages once a day. Perinatal treatment with ACTH (10 micrograms/kg/2x/day) altered several sexual behavior measurements, but did not have an overall effect on the number of males that exhibited sexual behavior. At a higher dose (500 micrograms/kg/2x/day) prenatal ACTH administration decreased sexual behavior in male rats, as measured by an increase in the percent of males that did not mount or intromit. In contrast, all males treated postnatally with ACTH (500 micrograms/kg/2x/day) completed 2 ejaculatory series and initiated a third series. No significant differences were observed in adult plasma testosterone or prolactin levels; however, serotonin levels in the preoptic area of adult male rats treated prenatally with ACTH (500 micrograms/kg/2x/day) were significantly higher than in prenatally treated saline males. In addition, an increase in plasma ACTH in adulthood was observed in animals injected postnatally with saline. This study indicates that the decrease in sexual behavior observed in males treated prenatally with ACTH is associated with increased serotonin levels in the preoptic area, which suggests that ACTH may act as a neuromodulator during sexual differentiation of the brain. It also demonstrates that the effect of perinatal manipulations on the development of male sexual behavior may vary depending on the ontogenetic period of the brain.     

Prostaglandin E2 accelerates sexual behavior in male rats

Sexual behavior in male rats is accompanied by an increase in body temperature of 18 degrees C. It has been suggested that this increase may be, at least in part, a febrile response mediated by the endogenous central release of prostaglandins of the E series (PGE). This putative release of PGE could also affect the expression of sexual behavior, a possibility that was tested in the present experiment. PGE2 was infused into the cerebral aqueduct and sexual behavior and hypothalamic temperature were monitored. PGE2 infusion raised hypothalamic temperature and decreased the postejaculatory interval and ejaculation latency. The exact cause of this acceleration of sexual behavior cannot as yet be determined.     

Ghrelin effects on gonadotropin secretion in male and female rats

Ghrelin is a 28-amino acid peptide primarily involved in the control of food intake and growth hormone secretion. The present experiments were carried out to analyze the potential involvement of ghrelin in the control of gonadotropin secretion. Prepubertal intact and gonadectomized female and male rats, cyclic rats in diestrus, lactating rats and aged female rats were i.c.v. injected with ghrelin (3 nmol/rat) and blood samples were obtained by decapitation 15 min later. In addition, we analyzed the effects of ghrelin on in vitro basal and luteinizing hormone-releasing hormone (LHRH)-stimulated gonadotropin secretion. Our present results indicate that ghrelin inhibited luteinizing hormone (LH) secretion in vivo in prepubertal males as well as gonadectomized males and females, whereas follicle-stimulating hormone (FSH) remained unaffected. In vitro, ghrelin stimulated the secretion of both gonadotropins, and differentially modulated the response to LHRH; the LH response was inhibited, while the FSH response was enhanced. Overall, our current data open up the possibility that ghrelin may be involved in the control of LH secretion, and in the dissociation of both gonadotropins that takes place in many physiological, pathological and experimental situations.     

Neonatal bonadal hormones: effect on maternal and sexual behavior in the male rat

Neonatal exposure of rats to androgen results in alteration of adult sex behavior and gonadotropin release. Other sexually dimorphic adult behaviors have also been shown to be dependent, either in part or in full, upon exposure to androgen neonatally. The present study was conducted to determine the effect of neonatal androgens in organizing the brain of the male rat (Long-Evans strain) with regard to maternal behavior. The results indicate that males neonatally exposed to androgen exhibit poor maternal behavior as adults when compared to males castrated at birth and males receiving gonadotropin antiserum in infancy. The males castrated at birth and males receiving gonadotropin antiserum in infancy, when primed with estrogen and progesterone, showed high levels of female sexual behavior when compared to controls. In terms of male sex behavior, the control groups performed slightly better than the males castrated at birth and males receiving antisera in infancy. The results suggest that the neonatal pituitary gland has an indirect role in the process of sexual differentiation.