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Biomedical subjects

G Rodríguez-Manzo

Publications and source records attributed to G Rodríguez-Manzo.

At least 19 recordsLinked to original sources

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.

Analysis of Variance↗

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.

Animals↗

Evidence for changes in brain enkephalin contents associated to male rat sexual activity.

Indirect evidence suggests that ejaculation might activate endogenous opioid systems, which exert an inhibitory influence on male rat sexual behaviour. The objective of the present study was to search for putative long-term changes in the contents of immunoreactive (IR) Met-enkephalin (IR-Met), Leu-enkephalin (IR-Leu) and opioid octapeptide Met--Arg(6)--Gly(7)--Leu(8) (IR-Oct) in specific brain areas, after the execution of different amounts of sexual activity. Additionally, basal contents of these enkephalins were compared between sexually active (SA) and persistent sexually inactive (SI) rats. Immunoreactivity to enkephalins was determined by radioimmunoanalysis, in the frontal cortex, the hypothalamus and midbrain of SA and SI rats, as well as 24 or 48 h after males had one ejaculation or copulated to exhaustion. Twenty-four hours after sexual activity, there was a generalised increase in enkephalin contents that returned to control values at the 48 h measurement in all brain areas, but the hypothalamus, where IR-Met and IR-Oct remained elevated. No differences in the magnitude of the changes were found between rats that ejaculated once and sexually satiated males. IR-Oct concentration in the hypothalamus of SI rats appeared significantly higher than in SA animals, with no differences in IR-Met and IR-Leu. Results give direct evidence of the activation of endogenous opioid systems by male rat sexual activity. The occurrence of long lasting increases in the contents of IR-Met and IR-Oct in the hypothalamus of rats that copulated was detected. Finally, an intrinsically elevated octapeptide concentration in the hypothalamus of SI rats was found.

Animals↗

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.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Gender differences in the cardiovascular responses to morphine and naloxone in spinal rats.

Putative gender differences in opiate cardiovascular effects were evaluated in spinal rats. After a 4-h exposure to a single dose of morphine (30 mg/kg, i.v.), abstinence was precipitated by naloxone (0.03-3 mg/kg, i.v.). Morphine produced a long-lasting bradycardia and a transient increase in arterial pressure that was similar in both genders. Thereafter, blood pressure decreased both in males and females. Naloxone precipitated a similar dose-dependent heart rate increase in both sexes and a gender-dependent increase in blood pressure. This sex difference appeared in the shape of the response. Prazosin (0.2 mg/kg), prior to naloxone, reduced the pressor response in all animals, suggesting a similar participation of the noradrenergic system in both genders. The present results extend to acute dependence the notion of a sex-dependent differential effect of morphine. The need to consider gender as a factor when studying the effects of opioids is highlighted.

Adrenergic alpha-Antagonists↗

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.

Animals↗

Stimulation of the medical preoptic area facilitates sexual behavior but does not reverse sexual satiation.

The aim of the present study was to establish whether electrical and/or drug stimulation of the medial preoptic area/anterior hypothalamus (mPOA/AH) surmounts the sexual behavior inhibition that results from copulation to exhaustion. Thus, intermittent electrical stimulation of the mPOA/AH (alone or combined with the systemic injection of yohimbine or apomorphine, at doses that were subthreshold for reversing sexual exhaustion) or intrapreoptic treatments to block GABAergic transmission were applied to sexually satiated rats. The results suggest that the mPOA/AH is not responsible for male sexual behavior inhibition or for the pharmacologically induced sexual behavior expression in satiated rats. Data are discussed in terms of the roles ascribed to the mPOA/AH, both in the control of sexual behavior expression and in the regulation of the postejaculatory interval.

Animals↗

Yohimbine interacts with the dopaminergic system to reverse sexual satiation: further evidence for a role of sexual motivation in sexual exhaustion.

The possible interaction of yohimbine with the dopaminergic system in the mediation of sexual behaviour expression in sexually exhausted male rats was investigated. The behavioural effects of the simultaneous injection of yohimbine (500 microg/kg) plus apomorphine (50 microg/kg) and those of the combined treatment of haloperidol (125 microg), a nonspecific dopamine receptor antagonist, with an effective dose of yohimbine (2000 microg/kg) on sexually satiated rats were evaluated. Data show that yohimbine and apomorphine, per se, dose-dependently reverse sexual exhaustion by increasing the percentage of sexually satiated rats copulating and resuming copulation after ejaculation. Injection of haloperidol simultaneous to an effective dose of yohimbine, blocked the ability of the latter to reverse sexual satiation. The combined treatment with subthreshold doses of apomorphine and yohimbine synergised to reverse the sexual inhibition characteristic of sexual exhaustion. Data suggest that the dopaminergic system might be the final pathway for the yohimbine-induced sexual behaviour expression in satiated rats. The possible role of sexual motivation in the sexual exhaustion phenomenon is discussed.

Adrenergic alpha-Antagonists↗

Anxiolytic-Like effect of ejaculation under various sexual behavior conditions in the male rat.

The purpose of the present study was to analyze the anxiety-like effect induced by ejaculation in male rats subjected to different sexual behavior conditions. The animal model of anxiety used was the conditioned defensive burying test. Results showed that experimental anxiety was reduced after one or six consecutive ejaculations. Six ejaculations did not induce a larger reduction in burying behavior than that produced by two, suggesting that this effect is not cumulative. This anxiolytic-like effect endured a short period (less than 24 h), and was not accompanied by a reduction in ambulatory behavior. The present results also showed a facilitating action of a previous ejaculation on the reduction in burying behavior induced by a second ejaculatory response. This potentiation occurred with an interval of 24 h between ejaculations. In sexually exhausted rats two populations are distinguished: one sexually unresponsive, and one achieving one ejaculation. Interestingly, in the ejaculatory population no reduction in burying behavior was observed, while in the unresponsive one a diminution in defensive burying was found. Data reveal differences in the anxiolytic-like properties of ejaculation between nonsatiated rats and the two populations of sexually exhausted animals.

Animals↗

8-OH-DPAT and male rat sexual behavior: partial blockade by noradrenergic lesion and sexual exhaustion.

As previously shown, the 5-HT1A agonist 8-OH-DPAT is a potent facilitator of male rat copulatory behavior in both sexually experienced and sexually exhausted male rats. The basis of this facilitation is still not clear. Therefore, the purpose of the present study was to determine whether 8-OH-DPAT-induced sexual-behavior facilitation could be counteracted by lesioning the NA system with the noradrenergic neurotoxin DSP4. In NA-lesioned, sexually experienced, non-exhausted rats, the facilitatory effects of 8-OH-DPAT on the number of mounts and the postejaculatory interval were reduced, the effect on the intromission latency disappeared, while the percentage of copulating rats was not significantly altered. In sexually exhausted rats bearing a lesion of the NA system, the facilitatory effects of 8-OH-DPAT on the percentage of copulating rats was blocked. Data are discussed on the basis of the interactions between the noradrenergic and serotonergic systems in the mediation of the facilitatory effect of 8-OH-DPAT in sexually exhausted and non-exhausted rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Opioid antagonists and the sexual satiation phenomenon.

This study evaluates the effects of the IP injection of naloxone (0.3, 3 and 30 mg/kg) and naltrexone (0.2, 2 and 20 mg/kg) on the sexual satiation phenomenon. It was found that both antagonists exert a dose-based biphasic effect on the proportion of sexually exhausted rats displaying copulation. The intermediate doses of both opioid antagonists were more effective than the low and high doses in increasing the percentage of animals engaged in copulation. The analysis of the specific sexual behaviour parameters revealed that naloxone produces a slight inhibitory effect at the lowest dose, evidenced as an increase in the intromission number. The higher doses of this compound facilitated copulation reflected as a shortening of the ejaculation latency and the interintromission interval (III) and an increase in the copulatory rate. Naltrexone treatment had only facilitatory effects at the lower doses by reducing the III. The higher doses of naloxone (3 and 30 mg/kg) and the intermediate dose of naltrexone (2 mg/kg) decreased the spontaneous ambulatory behaviour of sexually satiated rats without impairing sexual behaviour execution. Data suggest a participation of the endogenous opioid systems in the sexual inhibition resulting from sexual exhaustion.

Animals↗

Participation of the central noradrenergic system in the reestablishment of copulatory behavior of sexually exhausted rats by yohimbine, naloxone, and 8-OH-DPAT.

This study analyzes the impact of a neurotoxic lesion of the central noradrenergic system on the pharmacological reversal of the sexual inhibition present at sexual exhaustion, by IP treatment with yohimbine (2 mg/kg), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.25 mg/kg), and naloxone (3 mg/kg). All drugs, at the doses tested, were able to increase the percentage of sexually exhausted intact rats showing copulatory behavior 24 h after a sexual satiation session. In N-(2-chloroethyl)-N-ethyl-2-2-bromobenzylamine (DSP4)-lesioned, sexually exhausted animals, naloxone and 8-OH-DPAT lost their stimulatory effect on sexual behavior; yohimbine treatment was still able to markedly increase the percentage of satiated rats mounting, intromitting, and exhibiting the ejaculatory motor pattern, but inhibited seminal emission. The data strongly suggest that the integrity of the central noradrenergic system is essential for the pharmacological reestablishment of copulatory behavior in sexually exhausted rats. Results are in line with previous data showing that the sexual behavioral variables more directly addressing motivational components are severely affected by sexual satiation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Reversal of sexual exhaustion by serotonergic and noradrenergic agents.

The possible participation of the serotonergic and the noradrenergic systems in the control of the inhibitory state present during sexual satiation was studied from a pharmacological perspective. It was found that the 5-HT1A agonist 8-OH-DPAT and the alpha 2 adrenoceptor antagonist, yohimbine were effective in reversing the sexual inhibition resulting from sexual exhaustion. These findings show that the inhibition present during satiation is reversible and suggest that central mechanisms underlie it. The serotonergic as well as the noradrenergic systems, probably through their 5-HT1A and alpha 2 receptors, respectively, play a role in the establishment of this phenomenon. Additionally, the main features of the development of sexual exhaustion were reviewed. It was found that sexual exhaustion has two different expressions: a major proportion of the exhausted rats does not copulate and a third part of this population is able to execute one ejaculatory series from which they do not recover. The data are discussed in terms of the motivational and consummatory components of male sexual behaviour.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Further evidence showing that the inhibitory action of serotonin on rat masculine sexual behavior is mediated after the stimulation of 5-HT1B receptors.

To explore whether the inhibitory actions of endogenous serotonin on rat male sexual behavior were mediated via the stimulation of the 5-hydroxytryptamine1A (5-HT1A) or 5-HT1B receptor subtypes, two series of studies were undertaken. In the first series, an attempt to block the inhibitory actions of threshold doses of the serotonin precursor 5-hydroxytryptophan (5-HTP, 50 mg/kg) by administering the beta-5-HT antagonist alprenolol (5.0 mg/kg) and the selective beta-blocker practolol (0.5 mg/kg) was made. Both antagonists effectively prevented, at least partially, the inhibitory actions of 5-HTP. In the second series, a possible synergistic effect of a subthreshold dose of 5-HTP (12.5 mg/kg) with low doses of the selective 5-HT1B agonist 1-(m-trifluoro-methylphenyl)piperazine (TFMPP,0.125 mg/kg) or the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.0625 mg/kg) was investigated. A clear synergistic inhibitory effect of 5-HTP with TFMPP was observed. All data are interpreted based upon the hypothesis suggesting a physiological inhibitory role of the 5-HT1B receptor subtype on male rat sexual behavior.

5-Hydroxytryptophan↗

Effect of progesterone upon adenylate cyclase activity and cAMP levels on brain areas.

Changes induced by progesterone on adenylate cyclase activity and cAMP levels were determined in brain areas involved in the integration of sexual behavior in ovariectomized estradiol benzoate primed rats. Adenylate cyclase and cAMP concentrations were assayed in: preoptic area, ventromedial hypothalamus and cerebral cortex. Our results show a significant increase in both enzyme activity and cAMP levels at 2 and 4 hours after progesterone administration in all brain areas studied. These data suggest that the facilitatory effect of progesterone on sexual behavior involves an activating mechanism of this steroid upon the adenylate cyclase enzyme which results in an intraneuronal cAMP enhancement.

Adenylyl Cyclases↗

Effect of guanine derivatives on lordosis behavior in estrogen primed rats.

The effect of systemic administration of guanosine, cGMP, dipalmitoyl (dp) cGMP, 5'GMP and 5'GDP on lordosis behavior was studied in ovariectomized, estradiol benzoate (EB) primed rats (4 micrograms/rat). EB per se induced only weak lordosis behavior. Free cGMP (2.0 mg/rat); dp cGMP (1.0, 2.0 and 4.0 mg/rat) and 5'GMP (2.0 and 4.0 mg/rat) induced significant lordosis behavior in ovariectomized, estrogen-primed rats. Dp cGMP and 5'GMP (2.0 mg/rat), also induced lordosis behavior in ovariectomized, adrenalectomized estrogen primed rats. Lordosis behavior elicited with 2.0 mg/rat dp cGMP was blocked with 8.0 mg/rat methyl-isobutylxanthine (MIX), a phosphodiesterase inhibitor, suggesting that dp cGMP stimulated lordosis through its conversion to 5'GMP. Results are interpreted in terms of the activation of adenylate cyclase-cAMP systems by guanine nucleotides.

1-Methyl-3-isobutylxanthine↗

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.

Animals↗

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.

Animals↗