Lesions of the nucleus paragigantocellularis: effects on mating behavior in male rats

We evaluated the effects of bilateral radio-frequency lesions of the paragigantocellular (PGi) reticular nucleus in the ventral medulla on male rat copulatory behavior. In Experiment 1, sexually naive male rats with such lesions were more likely than sham-operated controls to copulate to ejaculation during their first exposure to an estrous female. Additionally, among the rats that copulated to ejaculation, those with lesions demonstrated a reduction in mount frequency (MF), intromission frequency (IF), and ejaculation latency (EL), and an increase in copulatory efficiency (CE). In Expt. 2, sexually experienced male rats were allowed to mate to sexual exhaustion. Males with PGi lesions showed an increased latency to sexual exhaustion and an increased number of ejaculations prior to exhaustion. Additionally, rats with PGi lesions displayed reductions in IF, EL, and post-ejaculatory interval (PEI) as they approached sexual exhaustion. Our results provide further evidence that the PGi is a supraspinal locus of descending inhibitory influence on spinal nuclei mediating ejaculatory reflexes in the male rat.     

Sexual behaviour is impaired by the abused inhalant toluene in adolescent male rats

Inhalant misuse is a worldwide problem, especially among adolescents. Toluene is the most widely misused inhalant. One hallmark of adolescence is the emergence of sexual behaviour, which can be affected by drug use. The aim of this study was to analyse the effects of toluene inhalation on different aspects of male rats’ sexual behaviour using a binge pattern of exposure in adolescent rats. Male Wistar rats were individually exposed to air or 6,000 ppm toluene for 30 min (acute exposure; n = 8 each) or twice a day for 12 days (repeated exposure; n = 9 each) in static exposure chambers. Independent groups of sexually experienced, adolescent rats (postnatal day 63, PN63) were tested after acute toluene exposure for copulation, sexual incentive motivation or noncontact erections. Sexually naïve, adolescent rats (PN45–59) were repeatedly exposed to toluene and tested for sexual behaviour after completing the 1st, 3rd, 5th, 7th, 9th, 11th and 13th exposure sessions. Acute toluene exposure impaired copulatory performance, diminished sexual incentive motivation and delayed noncontact erection occurrence in sexually experienced rats. Repeated toluene exposure during adolescence completely inhibited the onset of copulatory behaviours in sexually naïve rats, at the time at which they should have appeared. However, once the inhalant exposure ended, copulatory responses appeared gradually, and animals attained a typical, stable copulatory pattern. In conclusion, acute toluene exposure impairs sexual behaviour in young, sexually experienced animals, while repeated toluene exposure during adolescence prevents the onset of copulatory behaviour, although this effect is transitory.     

The possible involvement of the nonstrial pathway of the amygdala in neural control of sexual behavior in male rats

The effect of medial amygdala lesions on male sexual behavior in male rats with stria terminalis cut was examined. First, castrated male rats received bilateral transactions of the stria terminalis (STC) or sham cut (SC). Most STC males showed no ejaculation, but displayed mount and intromission, although the frequencies were not high compared to those of males with SC. Next, bilateral lesions of the medial amygdala (MAL) or sham lesion (SL) were performed in males with STC or SC. The MAL caused severe loss of all aspects of copulatory behavior in males with STC as well as in males with SC. The suppressive effect of the MAL on copulatory activity was stronger than that of the STC. These results indicate that a neural pathway other than the stria terminalis is involved in the regulation of male sexual behavior by the amygdala in male rats.     

Dopamine receptors in the ventral tegmental area affect motor, but not motivational or reflexive, components of copulation in male rats

Microinjection of apomorphine into the ventral tegmental area (VTA) of male rats was previously shown to delay the onset of copulation and slow its rate, presumably by stimulating impulse-regulating autoreceptors on cell bodies of the A10 mesocorticolimbic dopamine tract. Such stimulation would be expected to slow the firing rate of these neurons and, thereby, to impair locomotion and/or motivational processes. The present experiments tested whether the delayed onset and slowed rate of copulation were related to deficits in motor performance, sexual motivation, and/or genital reflexes. In X-maze tests the speed of running to all 4 goal boxes was slowed; however, the percentage of trials on which the male chose the female's goal box was not decreased. Examination of videotaped copulation tests revealed that the male showed fewer complete copulatory behaviors (mounts, intromissions, and ejaculations), but more misdirected or incomplete copulatory attempts after apomorphine in the VTA. There were also fewer scores of active, as opposed to inactive, behaviors, and the onset and rate of copulation were slowed. The total number of female directed behaviors was not different in apomorphine tests, compared to vehicle. Finally, tests of ex copula genital reflexes revealed no significant effects of apomorphine in the VTA on erections, penile movements, or seminal emissions. These data suggest a role of the VTA in the motor aspects and/or sensorimotor integration of copulation. Sexual motivation and ex copula genital reflexes appeared to be unaffected by apomorphine in the VTA.     

Effects of sexual behavioral manipulation on brain plasticity in adult rats

The purpose of the present study was to determine the effects of sexual behaviorial manipulation on brain plasticity in adult male rats. Adult male Sprague-Dawley rats that copulated during male sexual behavior testing were divided into four groups: control male; gonadectomized (Gdx) male; sexually active male; and sexually nonactive male. Female animals were used as an additional control group. At the end of a 12-week experimental period, the animals were again tested for male sexual behavior and tested for sexual motivation. Sexual behavior manipulations over the 12-week period resulted in significant differences in mount latency, mount frequency, intromission latency, intromission frequency, ejaculation latency, and the postejaculation interval. In the motivation test, significant differences in the number of approaches, contacts, and crossings of an electrified grid separating the test animal from a receptive female were also observed. Sexually dimorphic nucleus of the preoptic area (SDN-POA) volumes in sexually nonactive males were significantly smaller than in control males or sexually active males. Anteroventral periventricular nucleus (AVPV) volumes in the male groups were not significantly altered by sexual behavioral manipulations, however, the nonactive AVPV vol. was the only vol. not significantly different from the control female vol. These data demonstrate that in the adult rat, sexual behavioral manipulations resulted in significant alterations in behavior and in the vol. of the SDN-POA and that the effect of sexual behavior on the AVPV needs to be further investigated.     

Brain hyperthermia and temperature fluctuations during sexual interaction in female rats

Since the metabolic activity of neural cells is accompanied by heat release, brain temperature monitoring provides insight into behavior-associated changes in neural activity. In the present study, local temperatures were continuously recorded in several brain structures (nucleus accumbens, medial–preoptic hypothalamus and hippocampus) and a non-locomotor head muscle (musculus temporalis) in a receptive female rat during sexually arousing stimulation and subsequent copulatory behavior with an experienced male. Placement of the male into a neighboring compartment increased the female's temperature (0.8 °C) and additional, transient increases (0.2 °C) occurred when the rats were allowed to see and smell each other through a transparent barrier. Temperatures gradually increased further as the male repeatedly mounted and achieved intromissions, peaked 2–3 min after male's ejaculation (0.2–0.4 °C), and abruptly dropped until the male initiated a new copulatory cycle. Similar biphasic fluctuations accompanied subsequent copulatory cycles. Although both arousal-related temperature increases and biphasic fluctuations associated with copulatory cycles were evident in each recording location, brain sites showed consistently faster and stronger increases than the muscle, suggesting metabolic brain activation as the primary source of brain temperature fluctuations and a force behind associated changes in brain temperature. Robust brain hyperthermia and the generally similar pattern of phasic temperature fluctuations associated with individual events of sexual interaction found in males and females suggest widespread neural activation (motivational arousal) as a driving force underlying this cooperative motivated behavior in animals of both sexes. Females, however, showed different temperature changes in association with the initial (first mount or intromission) and final (ejaculation) events of each copulatory cycle, suggesting sex-specific differences in neural activity associated with the initiation and regulation of sexual behavior.     

Dose-dependent effects of acute kainic acid treatment on sexual behavior of male rats

Male rats of the Wistar strain were selected as good copulators (displaying at least 1 ejaculation in each of three consecutive tests for male sexual behavior) and sexually sluggish animals (displaying no ejaculations in each of three consecutive tests). The administration of low doses (1 and 2.5 mg/kg, i.p.) of kainic acid in sexually sluggish rats induced an enhancement of some parameters of copulatory behavior. In particular, significant reductions in latency to the first mount and intromission and increases in frequency of mounts and intromissions were observed. In contrast, the drug failed to exert any effect in good copulators. At the dose of 5 mg/kg (i.p.) kainic acid exerted an inhibitory effect on sexual behavior parameters both in good copulators and in sluggish rats. A persistent increase in latency to the first mount, intromission and ejaculation, and reduction in frequency of mounts, intromissions and ejaculation both in good copulators and in sluggish rats were observed 20 days after kainic acid treatment at the higher dose. No persistent effect of kainic acid 1 and 2.5 mg/kg was observed 20 days after treatment. These results suggest that kainic acid may affect in a dose-dependent manner several copulatory parameters of male sexual behavior repertoire. The bimodal effects could be explained considering a possible interaction of kainic acid with different neurotransmissions or receptor subtypes.     

Disruption of copulatory behavior of male rats by olfactory bulbectomy at two, but not ten, days of age

Male rats received bilateral olfactory bulbectomies or a sham operation at 2 days of age, 10 days of age, or in adulthood. Relative to sham-operated males, bulbectomy at 2 days of age or in adulthood reduced the proportion of males that copulated when tested as adults. In contrast, copulatory behavior was essentially normal in male rats bulbectomized at 10 days of age. The copulatory deficit in the Day-2 bulbectomized males was not a secondary effect of a testicular dysfunction because the age at preputial separation was normal and exogenous testosterone was ineffective in activating copulation in the noncopulating bulbectomized males. Neonatally bulbectomized males (both Day-2 and Day-10) showed a small, but significant, olfactory deficit when tested at 15 days of age, yet responded similarly to sham-operated males when tested in adulthood. Recovery of copulation after olfactory system damage appears to be dependent on the age of the animal at the time of the lesions. Furthermore, our results support previous suggestions that sparing of function is not a necessary consequence of the high plasticity of the developing nervous system.     

Dynamic increases in dopamine during paced copulation in the female rat

The role of dopamine in the rewarding aspects of sexual behaviour in female rats was investigated. This is a unique model because sexual behaviour is only rewarding when copulatory stimuli are experienced at the preferred rate of copulation for a female rat. In addition, increases in dopamine in the nucleus accumbens occur during sexual behaviour only when the female achieves this preferred rate of copulation. In this study, minute-by-minute changes in nucleus accumbens dopamine were monitored using in vivo microdialysis. We report here that extracellular dopamine in the nucleus accumbens increases before coital stimulation only when sexual behaviour is occurring under conditions that are rewarding to the female rat. We conclude that increases in dopamine in the nucleus accumbens are involved in anticipation, not consummation, of sexual behaviour in the female rat.     

Perinatal administration of nicotine alters subsequent sexual behavior and testosterone levels of male rats

The effect of pre- and/or postnatal administration of nicotine (0.25 mg/kg) on sexual behavior and testosterone levels in adult male rats was examined. Prenatal nicotine decreases male sexual behavior as measured by the number of males that mounted, intromitted or ejaculated. The males that did mount and/or ejaculate exhibited an increase in mount latency and number of mounts and a decrease in efficiency. This decrease was correlated with a decrease in plasma testosterone levels. Postnatal nicotine treatment improved the sexual performance of sexually naive males as measured by an increase in the number of males that completed 2 ejaculatory series and by a decrease in mount latency. This effect is transient, subsequent testing of the nicotine males eliminated this difference in sexual performance. Pre- and postnatal nicotine treatment did not affect the overall sexual performance of the male rats, although the number of mounts and intromissions during a second series decreased. Eye opening of male and female pups was accelerated with pre/postnatal nicotine administration. Birth weight, testis and levator ani weights, sex ration and number of pups per litter were not affected. We suggest that nicotine may act as a neuromodulator during sexual differentiation of the brain, demasculinizing the male progeny in rats. This effect is correlated with decreased testosterone levels during adulthood.     

Site-specific effects of anosmia and cloacal gland anesthesia on Fos expression induced in male quail brain by sexual behavior

In rats, expression of the immediate early gene, c-fos observed in the brain following male copulatory behavior relates mostly to the detection of olfactory information originating from the female and to somatosensory feedback from the penis. However, quail, like most birds, are generally considered to have a relatively poorly developed sense of smell. Furthermore, quail have no intromittent organ (e.g., penis). It is therefore intriguing that expression of male copulatory behavior induces in quail and rats a similar pattern of c-fos expression in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BSTM) and parts of the amygdala. We analyzed here by immunocytochemistry Fos expression in the mPOA/BSTM/amygdala of male quail that had been allowed to copulate with a female during standardized tests. Before these tests, some of the males had either their nostrils plugged, or their cloacal area anesthetized, or both. A control group was not exposed to females. These manipulations did not affect frequencies of male sexual behavior and all birds exposed to a female copulated normally. In the mPOA, the increased Fos expression induced by copulation was not affected by the cloacal gland anesthesia but was markedly reduced in subjects deprived of olfactory input. Both manipulations affected copulation-induced Fos expression in the BSTM. No change in Fos expression was observed in the amygdala. Thus immediate early gene expression in the mPOA and BSTM of quail is modulated at least in part by olfactory cues and/or somatosensory stimuli originating from the cloacal gland. Future work should specify the nature of these stimuli and their function in the expression of avian male sexual behavior.     

Excitotoxic lesions of the tegmental pedunculopontine nucleus impair copulation in naive male rats and block the rewarding effects of copulation in experienced male rats

The tegmental pedunculopontine nucleus (TPP) of the brainstem mediates food reward in food-sated animals and opiate reward in drug-naive animals. In the present study, we examine the effect of excitotoxic lesions of the TPP on sexual behaviour in naive and experienced male rats. Male, Long-Evans rats received either 0.25 micro L injections of NMDA (4.2 micro g/side) or vehicle (shams) into the TPP. In sexually naive males, complete bilateral TPP lesions decreased all measure of copulation (i.e. mounts, intromissions and ejaculations), prevented acquisition of conditioned sexual excitement, decreased approach preference for a receptive female over a non-receptive one, and decreased non-contact erections; unilateral or bilateral posterior-sparing TPP lesions did not affect any of these measures. Conversely, in sexually experienced males, lesions not only failed to disrupt copulation, but also increased conditioned sexual excitement, decreased post-ejaculatory interval and blocked the effect of prolonged copulation on conditioned sexual excitement. Following differential pairing of distinctive environments with and without copulation, sham males with sexual experience displayed a significant preference for the environment paired with copulation, whereas the lesion males with sexual experience displayed a significant aversion for the environment paired with copulation. These findings indicate that the TPP is critical for the acquisition of copulation in naive males and mediates the rewarding consequences of copulation in experienced males. Together these findings demonstrate that the TPP mediates sexual reward, but that sexual experience is not sufficient to produce a deprivation state.     

Chemosensory and steroid-responsive regions of the medial amygdala regulate distinct aspects of opposite-sex odor preference in male Syrian hamsters

In rodent species, such as the Syrian hamster, the expression of sexual preference requires neural integration of social chemosensory signals and steroid hormone cues. Although anatomical data suggest that separate pathways within the nervous system process these two signals, the functional significance of this separation is not well understood. Specifically, within the medial amygdala, the anterior region (MEa) receives input from the olfactory bulbs and other chemosensory areas, whereas the posterodorsal region (MEpd) contains a dense population of steroid receptors and receives less substantial chemosensory input. Consequently, the MEa may subserve a primarily discriminative function, whereas the MEpd may mediate the permissive effects of sex steroids on sexual preference. To test these hypotheses, we measured preference and attraction to female and male odors in males with lesions of either the MEa or MEpd. In Experiment 1, lesions of either region eliminated opposite-sex odor preferences. Importantly, MEpd-lesioned males displayed decreased attraction toward female odors, suggesting decreased sexual motivation. In contrast, MEa-lesioned males displayed high levels of investigation of both male and female odors, suggesting an inability to categorize the relevance of the odor stimuli. In Experiment 2, we verified that both MEa- and MEpd-lesioned males could discriminate between female and male odors, thereby eliminating the possibility that the observed lack of preference reflected a sensory deficit. Taken together, these results suggest that both the MEa and MEpd are critical for the expression of opposite-sex odor preference, although they appear to mediate distinct aspects of this behavior.     

Estrogen modulates neuronal movements within the developing preoptic area-anterior hypothalamus

The preoptic area-anterior hypothalamus (POA-AH) is characterized by sexually dimorphic features in a number of vertebrates and is a key region of the forebrain for regulating physiological responses and sexual behaviours. Using live-cell fluorescence video microscopy with organotypic brain slices, the current study examined sex differences in the movement characteristics of neurons expressing yellow fluorescent protein (YFP) driven by the Thy-1 promoter. Cells in slices from embryonic day 14 (E14), but not E13, mice displayed significant sex differences in their basal neuronal movement characteristics. Exposure to 10 nm estradiol-17beta (E2), but not 100 nm dihydrotestosterone, significantly altered cell movement characteristics within minutes of exposure, in a location-specific manner. E2 treatment decreased the rate of motion of cells located in the dorsal POA-AH but increased the frequency of movement in cells located more ventrally. These effects were consistent across age and sex. To further determine whether early-developing sex differences in the POA-AH depend upon gonadal steroids, we examined cell positions in mice with a disruption of the steroidogenic factor-1 gene, in which gonads do not form. An early-born cohort of cells were labelled with the mitotic indicator bromodeoxyuridine (BrdU) on E11. More cells were found in the POA-AH of females than males on the day of birth (P0) regardless of gonadal status. These results support the hypothesis that estrogen partially contributes to brain sexual dimorphism through its influence on cell movements during development. Estrogen's influence may be superimposed upon a pre-existing genetic bias.     

Individual differences in male rat ejaculatory behaviour: searching for models to study ejaculation disorders

In addition to investigating sexual function in rats that display normal ejaculatory behaviour, studying rats that are either 'hyposexual' or 'hypersexual' may provide important insights into the aetiology of ejaculatory dysfunctions in men, such as premature and retarded ejaculation. To this end, rats were matched into groups of 'sluggish', 'normal' and 'rapid' ejaculators based on their ejaculation frequencies displayed in a series of weekly sexual behaviour tests. Selecting rats on this parameter revealed large and stable differences in other parameters of sexual behaviour as well, including ejaculation latency and mount frequency but not intromission frequency and mount latency, putative indices of sexual motivation. Neuroanatomically, Fos immunoreactivity as a measure of neuronal activation was increased in rapid ejaculators compared with sluggish ejaculators in ejaculation-related brain areas, presumably associated with the differences in ejaculatory behaviour. Although the total number of oxytocin neurones within subregions of the hypothalamus did not differ between groups, in the supraoptic nucleus of the hypothalamus more oxytocin neurones were activated in rapid ejaculators compared with the other groups. Apart from the differences observed in ejaculatory behaviour, groups did not differ with respect to their locomotor activity and approach-avoidance behaviour as measured in the elevated plus-maze. Finally, apomorphine-induced stereotypy was similar in sluggish and rapid ejaculators, suggesting no large differences in dopamine susceptibility. Altogether, the present results suggest stable differences in male rat ejaculatory behaviour. Further exploring the neurobiological mechanisms underlying these differences may be a promising approach to gain insights into the aetiology of sexual dysfunctions such as premature, retarded or an-ejaculation.     

The medial preoptic area is involved in both sexual arousal and performance in male rats: re-evaluation of neuron activity in freely moving animals

A total of 74 single unit activities was recorded from the medial preoptic-anterior hypothalamic continuum (MPOA) during free copulatory behavior of male rats. Forty-six units (62.2%) showed changed activities during at least one phase of male copulatory movements; 26 units (35.1%) increased in the firing rate during pelvic thrusting; 32 units (43.2%) increased in activity during backward jumping immediately after intromission; only one unit (1.4%) showed decreased firing rate during thrusting and backward jumping; 12 units (16.2%) increased in activity during pursuit of a female; 19 units (25.7%) were suppressed during genital grooming. Furthermore, 67 units (90.5%) showed a significant change in activity throughout a series of copulatory behavior. From the introduction of a female up to ejaculation, relatively large number of units increased in the firing rate above the value during pre-introduction adaptation period. During postejaculatory interval, however, most units decreased in activity below the level during copulation. These results strongly suggest that the MPOA is involved in both sexual arousal and performance in male rats.     

The nature of the conditioned response mediating olfactory conditioned ejaculatory preference in the male rat

We have developed a model to study the influence of conditioning on sexual partner preference in the rat. In this model, pairing a neutral odor (almond) with copulation to ejaculation produces a subsequent preference to ejaculate with females bearing that odor. We refer to this phenomenon as a conditioned ejaculatory preference (CEP). The present study investigates the nature of the conditioned response that mediates CEP. Given equal mount and intromission distributions, but an unequal ejaculation distribution, we hypothesized that two mechanisms could account for CEP: facilitated ejaculation or selective ejaculation. To test these hypotheses, we examined the effect of omitting the olfactory conditioned stimulus (CS) or applying it to a nonreceptive female. Males trained with the CS paired with copulation (paired-trained males) failed to display evidence of delayed ejaculation when copulating with unscented females. Conversely, paired-trained males displayed CS-elicited copulatory behavior with CS-bearing nonreceptive females. In addition, we re-analyzed the data from the copulatory preference tests of previous experiments for CEP-displaying males. Again, we failed to find evidence of facilitated ejaculation with the scented female. However, the time between the last mount or intromission and ejaculation was increased if either occurred with the scented female. Furthermore, more mounts were directed towards the scented female near the end, but not at other points, of an ejaculatory series. These findings suggest that the paired-trained males attend to the scented female near the point of ejaculation, and are consistent with the hypothesis that CEP is mediated by selective ejaculation.     

Relationship between sexual behavior and sexually dimorphic structures in the anterior hypothalamus in control and prenatally stressed male rats

The present study was designed to examine the effects of prenatal stress on the morphological development of sexually dimorphic structures in the anterior hypothalamus in male rats and to determine if there is a relationship between morphologic development of the brain and copulatory behavior in individual animals. Dams in the stress group were subjected to treatments of heat-light restraint during the third trimester of gestation (day 14 to parturition) three times daily for 45-min periods. At 90 days of age, prenatally stressed and control male offspring were tested during the dark cycle for spontaneous male sexual behavior. Volumes of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anteroventral periventricular nucleus (AVPV) were measured. Comparisons were made between copulatory behavior and hypothalamic nuclear volumes. SDN-POA volumes were significantly reduced (feminized; males have a larger SDN-POA than females) in prenatally stressed males that did not copulate, whereas, SDN-POA volumes in prenatally stressed males that copulated were not altered. The few control males that did not copulate (sexually non-active) also had significantly reduced SDN-POA volumes compared to the control males that did copulate (sexually active). The volume of the AVPV was significantly increased (feminized; males have a smaller AVPV than females) in prenatally stressed males that were sexually non-active compared to AVPV volumes in sexually active males. The results obtained in this study provide a strong positive relationship between sexual behavior and the morphology of the two sexually dimorphic structures measured.     

Effects of nucleus accumbens lesion on female rat sexual receptivity and proceptivity in a partner preference paradigm

A partner preference paradigm, stud male vs estrous female, was used to study sexual behavior. Ovariectomized Wistar rats received bilateral electrolytic (n = 33) or sham (n = 16) lesion of the nucleus accumbens. Animals were tested in two different experimental situations, either with stimulus animals tethered (test with possibility of mating) or with stimulus animals behind a wire mesh (test without possibility of mating). Each test was carried out once prior to surgery and twice postoperatively following priming with estradiol benzoate and progesterone. Lordosis, rejection behaviors and soliciting patterns were scored in tests with tethered stimulus animals. The tendency of the experimental female to approach and remain in the vicinity of each stimulus animal was quantified to study the partner preference. Nucleus accumbens lesion increased the number of rejection responses to male mount attempts without modifying either receptivity estimated by lordosis reflex or soliciting behaviors. Control females showed a statistically significant preference for the male throughout the experiments. Lesioned females exhibit a preference for the male only in the test without sexual interaction possibility. This preference disappeared in the test with possibility of mating and it was even reversed when the male showed copulatory activity. These results, together with the absence of changes in lordosis behavior and soliciting activity, suggest that both the inversion in preference and the higher levels of mount rejections found in the lesioned animals are more likely attributable to hyperreactivity to the copulatory stimulus rather than an alteration in the female's rat sexual motivation.