Gabriela Rodríguez-Manzo

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.

Evidence for the involvement of a spinal pattern generator in the control of the genital motor pattern of ejaculation

One of the hypotheses to explain the neural mechanisms underlying rhythmic behaviours suggests that the central nervous system has the intrinsic capacity to produce repetitive, rhythmic output to the muscles involved in the response by means of a neuronal circuit named central pattern generator (CPG). The occurrence of rhythmic motor patterns during ejaculatory behaviour in mammals, which includes the genital motor pattern, has been shown. A CPG might regulate the timing of the repetitive muscular responses that constitute the ejaculatory motor pattern. The objective of the present study was to evidence that a CPG at a spinal level is involved in the expression and pacing of the rhythmic motor pattern generated during ejaculation. To this purpose we used the genital reflex as a model system. Following the general principles for the study of rhythmic motor patterns, the data obtained in the present series of experiments document that: (1) a rhythmic muscular response, the genital motor pattern, is registered during the ejaculatory event (expulsion of the urethral contents); (2) this ejaculatory motor response has similar EMG characteristics in intact and in spinal urethane-anaesthetised male rats; (3) interruption of the afferent inflow (deafferentation) does not disrupt the expression of the ejaculatory motor train; (4) a change in the stimulation interval does not alter the intrinsic pacing of the ejaculatory-like response; and (5) fictive ejaculation can be induced by pharmacological means. Together, this evidence supports the notion that a CPG produces the rhythmic ejaculatory motor pattern registered during fictive ejaculation.

The spinal pattern generator for ejaculation.

Ejaculation is the physiological process that describes the expulsion of the semen from the urethra. This physiological response is a remarkably sophisticated phenomenon that requires the participation of several stereotyped motor patterns for its expression and when taking place, it starts a constellation of short- and long-lasting physiological and behavioural processes. Little is known about the neural mechanisms accounting for its activation. It has been recently proposed that a central pattern generator located at the spinal level is involved in the control of ejaculation. The aim of this paper is to review the evidence supporting this notion. Thus, the mechanics of ejaculation, its anatomical substrates and innervation are described. Besides, evidence from behavioural, physiological and pharmacological studies that support the existence of an intraspinal rhythm modulating the ejaculatory response are provided. Data are discussed in the context of the physiology of male sexual function.

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.

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.

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.

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.

Stimulation of the medial 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.

Sexual behavior reduces hypothalamic androgen receptor immunoreactivity

Male sexual behavior is regulated by limbic areas like the medial preoptic nucleus (MPN), the bed nucleus of the stria terminalis (BST), the nucleus accumbens (nAcc) and the ventromedial hypothalamic nucleus (VMN). Neurons in these brain areas are rich in androgen receptors (AR) and express FOS-immunoreactivity in response to mating. In many species sexual satiation, a state of sexual behavior inhibition, is attained after multiple ejaculations. The mechanisms underlying sexual satiation are largely unknown. In this study we show that sexual activity reduces androgen receptor immunoreactivity (AR-ir) in some of the brain areas associated with the control of male sexual behavior, but not in others. Thus, one ejaculation reduced the AR-ir in the MPN and nAcc, but not in the BST and VMN. Copulation to satiation, on the other hand, reduced AR-ir in the MPN, nAcc and VMN, and not in the BST. The AR-ir reduction observed in the MPN of sexually satiated rats was drastic when compared to that of animals ejaculating once. Serum androgen levels did not vary after one ejaculation or copulation to exhaustion. These data reveal that sexual activity reduces AR in specific brain areas and suggest the possibility that such a reduction underlies the sexual inhibition that characterizes sexual satiety.

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.