Ejaculatory training lengthens the ejaculation latency and facilitates the functioning of the spinal generator for ejaculation of rats with rapid ejaculation.

A spinal pattern generator controls the ejaculatory response. Central pattern generators (CPGs) may be entrained to improve the motor patterns under their control. In the present study we tested the hypothesis that training of the spinal generator for ejaculation (SGE) by daily copulation until ejaculation, could promote substantive changes in its functioning permitting a better SGE control of the genital motor pattern of ejaculation (GMPE) and, as a consequence, a normalization of the ejaculation latency of rats with rapid ejaculation. To that aim, we evaluated in sexually experienced male rats with rapid ejaculation (1) the effects of daily copulation to ejaculation, following different entrainment schedules, on their ejaculation latencies, (2) the impact of these different ejaculatory entrainment schedules upon the parameters of the GMPE and (3) the possible emergence of persistent changes in the functioning of the SGE associated to the daily ejaculation entrainment schedules. The data obtained show that intense ejaculatory training of rats with rapid ejaculation lengthens the ejaculation latency during copulation and augments the ejaculatory capacity of the SGE in this population when spinalized. Thus, present data reveal that like other CPGs, the SGE can be trained and put forward that training of the SGE by daily copulation to ejaculation might be a promising alternative that should be taken into consideration for the treatment of premature ejaculation.

Huperzia saururus Lam. Trevis. (Lycopodiaceae) facilitates ejaculation in spinal cord transected male rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Huperzia saururus (Lam.) Trevis. has an extensive ethnopharmacological use, mainly because of its aphrodisiac properties. The species is consumed as decoctions or infusions in traditional medicine. The purpose of the present research was to determine if Huperzia saururus is able to increase sexual potency by evaluating the ejaculatory response, in the presence of a decoction in spinal cord transected male rats. MATERIALS AND METHODS: The fictive ejaculation model to record the rhythmic contractions of the bulbospongiosus muscles that accompany ejaculation as an indicator of ejaculation occurrence was used. Sexually experienced male Wistar rats were used. The activation of the fictive ejaculation by the i.v. administration of a decoction was tested, as well as the effects of the oxytocinergic, cholinergic, adrenergic and nitrergic antagonism upon the pro-ejaculatory activity of Huperzia saururus. RESULTS: Decoction (3µg/animal) was able to activate the fictive ejaculation in spinal male rats, producing a statistically significant diminution on the latency of discharge parameter and a statistically significant augment for the number of discharges. Moreover, when sequential treatments using antagonists plus decoction were administered, the effects produced showed that prazosin prevent the pro-ejaculatory effect of the decoction and that the four antagonists assayed blocked the facilitatory effect of Huperzia saururus since the facilitation in the latency of response was prevented, and the number of discharges was reduced. Together these findings support the notion that the decoction exerts an aphrodisiac effect influencing the ejaculatory potency which is partially mediated by oxytocinergic, cholinergic, adrenergic and nitrergic spinal mechanisms. CONCLUSION: In agreement to the ethnopharmacological uses, Huperzia saururus decoction has aphrodisiac properties by influence on the ejaculatory potency.

Effects of Dracaena arborea (Dracaenaceae) on sexual dysfunction in 4 weeks hyperglycemic male rats.

OBJECTIVE: To investigate the effects of Dracaena arborea (D. arborea) on the sexual behavior parameters in experienced type-1 diabetic rats. METHODS: Aqueous and ethanol (100 and 500 mg/kg respectively) extracts of dried root barks of D. arborea, sildenafil citrate (1.44 mg/kg), trimethylamine-N-oxide (TMAO, 20 mg/kg) and distilled water (10 mL/kg) were orally administered to 4 weeks streptozotocin-induced diabetic rats. Mount latency and frequency (ML, MF), intromission latency and frequency (IL, IF) and post-ejaculatory interval (PEI) were measured by ejaculatory series during 90 min once a week for 4 weeks. Glycemia was determined at the beginning and at the end of the treatment. RESULTS: D. arborea did not show any major antihyperglycemic effects. Compared to the control group, a significant (P<0.05-0.001) increase in MF and IF was noticed in rats treated with sildenafil citrate (89.71% and 90.07% respectively), aqueous (500 mg/kg, 88.08% and 88.74% respectively) and ethanol (100 mg/kg; 89.53% and 89.17 respectively) extracts of D. arborea after two weeks (series 1) of treatment. ML, IL and PEI were significantly (P<0.05-0.001) decreased after 4 weeks of daily treatment [sildenafil citrate (96.31, 96.31% and 34.98%), and D. arborea aqueous 500 mg/kg (94.33, 94.33% and 66.60%) and ethanol extracts 100 mg/kg (96.98, 97.08% and 64.26%)]. CONCLUSIONS: These aphrodisiac potentials of D. arborea in experienced diabetic rats could be due to the antioxidant and androgenic properties of phenols, flavonoids, saponins and sterols revealed in the plant extracts.

Dracaena arborea extracts delay the pro-ejaculatory effect of dopamine and oxytocin in spinal male rats.

Dracaena arborea is a medicinal plant with ethnopharmacological aphrodisiac reputation. In the present study, the effect of an intravenous administration of aqueous and ethanolic extracts from the dried roots of this plant on the ejaculatory pattern of spinal cord-transected and urethane-anaesthetized rats was investigated. In addition, the effects of these extracts were also determined on dopamine and oxytocin-induced ejaculation. Systemic administration of aqueous and ethanolic extracts (5, 20, 60, 100 mg kg(-1)) of D. arborea did not activate fictive ejaculation, whereas dopamine (0.1 µM kg(-1)) and oxytocin (0.5 UI kg(-1)) provoked ejaculation evidenced by the rhythmic contractions of the bulbospongiosus muscles accompanied with penile erection and sometimes with expulsion of the seminal plugs. Pretreatment of spinal rats with D. arborea extracts dose-dependently blocked the pro-ejaculatory activity of dopamine and oxytocin. In conclusion, the present study shows that the bioactive substances present in the extracts of D. arborea inhibit the activity of the bulbospongiosus muscles through the blockade of dopaminergic and oxytocinergic receptors in rats.

Effects of bupropion on the ejaculatory response of male rats.

Chronic antidepressant treatment is associated with sexual side effects, particularly affecting the ejaculatory response. Bupropion (BP), an antidepressant inhibiting dopamine/noradrenaline reuptake, seems to have a low impact upon male sexual function. Ejaculation is regulated both at the brain and spinal cord by the spinal generator for ejaculation (SGE). We investigated the effects of chronic BP treatment on ejaculatory behavior and on SGE functioning. Sexually experienced male rats were intraperitoneally (i.p.) injected with BP (7.5 or 15 mg kg(-1)) during 14 days and tested for sexual behavior on days 1, 7 and 14 of treatment; these same males were used to evaluate the functioning of the SGE by recording the genital motor pattern for ejaculation (GMPE). Acute and chronic BP administration did not importantly modify copulatory behavior of male rats. Chronic treatment with the low dose of BP produced deficits in the functioning of the SGE that were restored by activation of the SGE through afferent stimulation. Conversely, chronic treatment with the high-dose of BP disrupted the functioning of the SGE, as the deficits were not compensated by activating the SGE through sensory stimulation. It is concluded that chronic BP at high doses alters the functioning of the SGE.

Rhythmic motor patterns accompanying ejaculation in spinal cord-transected male rats.

A spinal pattern generator controls the ejaculatory response. Activation of this spinal generator elicits rhythmic motor patterns of the striated musculature that surrounds the genital tract that contributes to the expulsion of seminal secretions. In the present study, we elicited ejaculation in spinal cord-transected male rats by mechanically stimulating the urethra and registered rhythmic motor patterns in the cremasteric, iliopsoas and pubococcygeus muscles. The rhythmic motor activity recorded in these muscles was compared with that elicited in the bulbospongiosus muscles; the results revealed similarities in the motor parameters among all the muscles. Data of this study, showing the occurrence of rhythmic motor behaviour in the cremasteric, iliopsoas and pubococcygeus muscles during ejaculation, suggest that these muscles might be under the control of the spinal generator for ejaculation.

Pro-sexual effects of Turnera diffusa Wild (Turneraceae) in male rats involves the nitric oxide pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Turnera diffusa Wild has been used in folk medicine by its aphrodisiac and tranquilizing properties. Previously we experimentally showed the aphrodisiac effect of a chemically characterized aqueous extract of Turnera diffusa in male rats. However, the mechanism of action underlying such effects has not been studied. STUDY AIMS: As part of our systematic studies of pharmacological properties of Turnera diffusa, we aimed to analyze whether the increased sexual motivation and the augmented sexual performance of sexually sluggish (SL) male rats treated with Turnera diffusa involves the NO pathway. Additionally we analyzed whether such effects were exerted at the level of the brain or the spinal cord. Finally, anxiety levels and ambulatory activity were also evaluated. MATERIAL AND METHODS: Turnera diffusa (10-40 mg/kg) and sildenafil citrate (10 mg/kg) with or without a nonspecific inhibitor of NO synthase, Nω-nitro-L-arginine methyl esther (L-NAME, 12.5 mg/kg) were evaluated in SL rats, in a standard sexual behavior test and in the fictive ejaculation model in spinal cord transected and urethane-anaesthetized SL rats. Anxiety levels or ambulation were assessed in the burying behavior and open-field tests. RESULTS: Turnera diffusa and sildenafil (both at 10 mg/kg) facilitated expression of male sexual behavior by shortening mainly ejaculation latency. Treatments also facilitated the number of discharges in the ejaculatory motor pattern as well as the number of ejaculatory motor patterns and its associated penile erections. L-NAME prevented the pro-sexual effects of treatments on both experimental models. Besides, the extract of Turnera diffusa (10 mg/kg) produced an anxiolytic-like effect in male rats without affecting ambulation. CONCLUSIONS: Findings from the present work support the notion that pro-sexual effect of the aqueous extract of Turnera diffusa in rats involves the participation of NO pathway, mainly at central level. The anxiolytic-like effect of Turnera diffusa is an advantage to its use for improving sexual performance.

DMI-induced sexual effects in male rats: analysis of DMI's acute and chronic actions on copulatory behavior and on the genital motor pattern of ejaculation.

Desipramine (DMI) is a tricyclic antidepressant that alters male sexual function. This work was designed to study the effects of acute and chronic DMI treatments on male rat copulatory behavior, discriminating between spinal and behavioral DMI actions on the ejaculatory response. To this aim, sexually experienced male Wistar rats received DMI (7.5 or 15 mg/kg, i.p.) for 14 days and were tested for sexual behavior on Days 1, 7 and 14 of treatment. Besides, the genital motor pattern of ejaculation (GMPE) was recorded in anaesthetized, spinal male rats after acute (1-10 microg, i.v.) or 14-day chronic DMI (15 mg/kg, i.p.) treatment. Results showed that acute and chronic DMI treatments reduced the ejaculatory threshold by decreasing intromission number and ejaculation latency of male rats, in successive copulatory series. The intensity of the effects depended on the dose and treatment duration. DMI acute treatment activated GMPE expression only at the lower doses and these responses exhibited modified parameters. Chronic DMI reduced the number of discharges and increased the frequency of discharge of spontaneous GMPE responses, affected mechanically evoked ones and increased the number of GMPEs expressed after repeated genital stimulation as compared to control rats. DMI treatments affected copulatory behavior both at brain and spinal levels and its effects on ejaculation, assumed to be similar in behavioral and spinal models, differed.

Increase of ejaculatory capacity by systemic administration of the oquichpatli (Senecio cardiophyllus) aqueous crude extract in male rats.

AIM OF THE STUDY: To analyse the pro-ejaculatory properties of the proverbial Mexican plant oquichpatli, Senecio cardiophyllus, in an animal model for the study of ejaculation in spinal and anaesthetised male rats. MATERIALS AND METHODS: The aqueous crude extract of Senecio cardiophyllus (at 0.4, 1.2 and 4 mg/kg) was i.v. administered to (a) anaesthetised and spinalised male rats after spinal cord transection and (b) anaesthetised and spinalised male rats previous to the inhibition of ejaculation elicited by repeated urethral stimulation. The motor pattern of ejaculation and the development of its inhibition were analysed under the influence of the aqueous crude extract of Senecio cardiophyllus and compared to urethrally induced ejaculations. RESULTS: Systemic administration of the Senecio cardiophyllus aqueous crude extract, at all tested doses, induced the ejaculatory response in male rats. This response was featured by a statistically significant augmented number of ejaculatory discharges when compared to control animals. Oquichpatli-induced ejaculatory responses included the expression of autonomic and motor components of ejaculation and the potent expulsion of urethral contents and seminal plugs. Administration of oquichpatli aqueous crude extract prevented the inhibition of ejaculation elicited by urethral stimulation by promoting a statistically significant increase in the expression of ejaculatory motor patterns. CONCLUSION: Present findings show by the first time that the aqueous crude extract of Senecio cardiophyllus possesses the ability to increase the ejaculatory capacity in male rats.

Evidence for the presence of the spinal pattern generator involved in the control of the genital ejaculatory pattern in the female rat.

Substantial progress has been made during recent years in elucidating the control of male ejaculatory function by the central nervous system. These efforts have revealed the participation of a central pattern generator in the control of ejaculation. There is a strong similarity in the neural organization of male and female sexual functions. In the present study, the hypothesis that the spinal generator for ejaculation was present and functional in the female rat was evaluated. To this purpose, the expression of the ejaculatory motor pattern and its pharmacological activation in spinally transected female rats were investigated. Results revealed the presence in females of the already described rhythmic ejaculatory motor pattern of male rats. This ejaculatory motor pattern could be registered in the urethralis muscle of the female rat after mechanical stimulation of the urethra, vagina and clitoris and consisted, as in the male rat, of a first ejaculatory motor train followed by an after-discharge component. Besides, the female genital ejaculatory motor pattern could be pharmacologically induced by the systemic injection of sodium nitroprusside with similar motor characteristics. No significant differences between the sensorial and pharmacologically induced female genital motor patterns were found. Present findings provide evidence for the presence of the genital motor pattern of ejaculation in female rats and suggest that the spinal generator for ejaculation is also present and functional in this gender.

alpha-Adrenergic agents modulate the activity of the spinal pattern generator for ejaculation.

Spinal cord transection at a thoracic level activates fictive ejaculation (FE) in the male rat. It has earlier been demonstrated that fictive motor patterns may be activated by pharmacological means and that the noradrenergic system seems to be particularly efficient in triggering locomotor fictive patterns in spinal animals. In the present study, the hypothesis was tested that the spinal noradrenergic system participates in the activation of the spinal generator for ejaculation (SGE). To this aim, the effect of the adrenergic agents, methoxamine, prazosin, clonidine, and yohimbine, upon FE was evaluated in spinal male rats using electromyographic techniques. The results obtained show that ejaculatory rhythmic patterns, accompanied by the expulsion of urethral contents and phasic penile movements, can be elicited by the intravenous (i.v.) injection of methoxamine or yohimbine. These drug-induced motor sequences appear superimposed to the intrinsic ejaculatory spinal rhythm. By contrast, i.v. injection of prazosin or clonidine blocked the expression of the spontaneous ejaculatory rhythmic pattern without inducing any other genital response. These data suggest that an increased noradrenergic tone, either by blockade of presynaptic alpha2-adrenoceptors or by stimulation of postsynaptic alpha1-adrenoceptors, results in the activation of the SGE. Present findings provide the evidence that the SGE might be importantly influenced by the noradrenergic system, which exerts a facilitatory control on the expression of the genital motor pattern of ejaculation.

Evidence for the presence and functioning of the spinal generator for ejaculation in the neonatal male rat.

A spinal pattern generator controls ejaculation in the male rat. In the present study, the hypothesis that the spinal generator for ejaculation was functional at early postnatal stages was evaluated. To this purpose, the expression of the ejaculatory motor pattern and its pharmacological activation in spinally transected neonatal rats from postnatal day 2 to weaning were investigated. Results revealed the presence of the rhythmic ejaculatory motor pattern in neonatal male rats. As in adult sexually experienced animals, the neonatal ejaculatory motor pattern could be elicited after the application of an ejaculation-like-releasing stimulus. The rhythmic genital motor response of neonates exhibited a gradual maturation that was reflected in its motor parameters until showing the features of the adult response at postnatal day 28. Besides, the ejaculatory motor pattern could be induced by the systemic injection of oxytocin in 7-day-old neonates as well as in adult animals. Present findings provide evidence for the presence of the spinal generator for ejaculation early during postnatal development, suggesting that its organisation is innate.

Role of genital sensory information in the control of the functioning of the spinal generator for ejaculation.

An intrinsic spinal rhythm mediates fictive ejaculation (FE). In this study, the effect of genital sensory stimulation on the functioning of the spinal generator of ejaculation was investigated. To this aim, the effect of (a) stimulation of internal and external genital structures; (b) repeated elicitation of FE and (c) genital stimulation during in progress expression of FE on the rhythmic genital motor pattern of ejaculation (GMPE) was analysed in sexually experienced, spinal male rats. Results showed that the spinal intrinsic ejaculatory rhythm can be modulated by genital inputs, and that repeated stimulation modifies this rhythm, progressively inhibiting its expression. Finally, in progress GMPEs could be reset by overlapping genital stimulation, supporting the notion of the spinal cord mediating the inhibition of FE following repeated genital inflow. Results reveal the nature of the modulatory role that genital afferent information exerts on the expression of FE.

Aphrodisiac properties of Montanoa tomentosa aqueous crude extract in male rats.

Cihuapatli, the Mexican zoapatle (Montanoa tomentosa) has an extensive ethnomedical history of use as a traditional remedy for reproductive impairments. During the study of the ejaculatory function in rats and by testing a set of Mexican plants with medicinal properties, we observed that crude extracts of M. tomentosa facilitated ejaculation. Thus, we decided to analyze the possibility that this plant possessed sexual stimulant properties. To that aim, copulatory behavior of sexually active male rats receiving doses of 38, 75 and 150 mg/kg of the aqueous crude extract of M. tomentosa, as it is prepared in traditional medicine, was assessed. In addition, we evaluated the effect of the 75-mg/kg dose of the extract on males with anesthetization of the genital area and on sexual behavior of sexually inactive male rats (noncopulators). Results showed that acute oral administration of crude extracts of M. tomentosa facilitates expression of sexual behavior in sexually active male rats, significantly increases mounting behavior in genitally anesthetized animals and induces the expression of sexual behavior in noncopulating males. Altogether, these data reveal a facilitatory action of this extract on sexual activity and particularly on sexual arousal. Present findings provide experimental evidence that the crude extract preparation of M. tomentosa, used as a traditional remedy, possesses aphrodisiac properties.

Exhaustion of the coital reflex in spinal male rats is reversed by the serotonergic agonist 8-OH-DPAT.

Previous studies from our laboratory have shown that the genital motor pattern associated to the coital reflex in spinal male rats becomes exhausted when repeatedly evoked. Exhaustion of the genital motor pattern could be related to the sexual exhaustion phenomenon observed in copulating male rats. The present study was aimed to describe the features of coital reflex exhaustion and to determine if the 5-HT1A agonist 8-OH-DPAT was able to reverse exhaustion of this ejaculatory-like response. Additionally, the effect of pre-treatment with the 5-HT1A antagonist WAY 100635 on the 8-OH-DPAT induced motor response was evaluated. Results revealed that development of coital reflex exhaustion initiated with a progressive increase in the latency of response and was characterised by a change in the properties of the motor pattern itself. Once exhausted, i.v. administration of 8-OH-DPAT provoked the immediate expression of a potent motor pattern similar to the coital reflex, but in the absence of urethral stimulation. Injection of WAY 100635 induced, per se, expression of the coital reflex after exhaustion. Notwithstanding, pre-treatment with WAY 100635 was able to block the 8-OH-DPAT-induced motor response implying that its effect was exerted upon 5-HT1A receptors. Data suggest that the sexual exhaustion phenomenon might possess a spinal component.

Sensory and motor aspects of the coital reflex in the spinal male rat.

In the present study the sensory and motor aspects of the coital reflex model in male rats were evaluated. Electromyographic reflex activity after mechanical stimulation of the urethra, penis and scrotal skin was recorded in all genital muscles. The possibility that a facilitatory mechanism of these muscular responses was located in the rat spinal cord was evaluated by removing the genital afferents. Results showed that urethral, penile and scrotal stimulation evoked the coital reflex in all genital muscles. Similarly, coital responses were obtained spontaneously in deafferentated animals. The parameters among the motor patterns evoked with the different mechanical stimuli were very similar. Parameters of spontaneous motor patterns were not importantly different from those obtained reflexively. A conspicuous difference between these responses was the presence of an after-discharge activity in genitally-stimulated animals. Additionally, it was found that this motor pattern can be exhausted with repeated stimulation. Spontaneous responses did not show the exhaustion phenomenon. Results are discussed in the context of the sensory-motor aspects of male sexual behaviour.