RESUMO
Animal studies and clinical investigations reveal that serotonin plays a central role in the control of the ejaculatory threshold. The chronic use of selective serotonin reuptake inhibitors (SSRIs) frequently results in sexual dysfunction, inviting to analyze the modulatory actions of serotonin on male sexual function in depth. Even though the main effect of serotonin on male sexual responses is inhibitory, this neuromodulator also mediates brief important stimulatory actions. Serotonin (5-HT) can activate two intracellular signaling pathways: a lower-threshold facilitatory pathway, and a higher-threshold inhibitory pathway, leading to biphasic effects. We propose that these divergent actions are related to the stimulation or inhibition of glutamatergic and GABAergic interneurons. Experimental evidence suggests that low 5-HT concentrations produce stimulatory actions on male ejaculatory aspects that might be mediated by the blockade of the GABAergic neurotransmission in the MPOA and spinal cord, which in turn releases a tonic inhibition that allows other neurotransmitters such as glutamate, noradrenaline, oxytocin and dopamine to initiate a sequence of molecular events resulting in the expression of ejaculation. Similar serotonin actions, mediated via interneurons, have been proposed for the regulation of other processes and occur in many central nervous system areas, indicating that it is not an isolated phenomenon.
Assuntos
Encéfalo/efeitos dos fármacos , Receptores de Serotonina/metabolismo , Serotonina/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Ácido Glutâmico/metabolismo , Masculino , Ratos , Serotonina/metabolismo , Serotoninérgicos/farmacologia , Comportamento Sexual Animal/fisiologia , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologiaRESUMO
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.
Assuntos
Bupropiona/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Ejaculação/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Masculino , Atividade Motora , RatosRESUMO
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.
Assuntos
Animais Recém-Nascidos/fisiologia , Ejaculação/fisiologia , Neurônios Motores/fisiologia , Músculos/inervação , Medula Espinal/citologia , Medula Espinal/fisiologia , Animais , Ejaculação/efeitos dos fármacos , Eletromiografia , Masculino , Ocitocina/administração & dosagem , Estimulação Física , Ratos , Ratos Wistar , Medula Espinal/cirurgia , Uretra/fisiologiaRESUMO
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.
Assuntos
Ejaculação/fisiologia , Genitália Masculina/fisiologia , Medula Espinal/fisiologia , Animais , Masculino , Estimulação Física , Ratos , Ratos Wistar , Medula Espinal/cirurgia , Uretra/fisiologiaRESUMO
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.
Assuntos
Afrodisíacos/farmacologia , Montanoa , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Afrodisíacos/isolamento & purificação , Feminino , Flores , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta , Ratos , Ratos Wistar , Comportamento Sexual Animal/fisiologia , Água/farmacologiaRESUMO
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.
Assuntos
Química Encefálica/fisiologia , Encefalinas/metabolismo , Comportamento Sexual Animal/fisiologia , Animais , Encefalina Leucina/metabolismo , Encefalina Metionina/metabolismo , Encefalinas/análise , Lobo Frontal/química , Lobo Frontal/metabolismo , Hipotálamo/química , Hipotálamo/metabolismo , Masculino , Mesencéfalo/química , Mesencéfalo/metabolismo , Radioimunoensaio , RatosRESUMO
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.
Assuntos
8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Copulação/fisiologia , Estado de Descerebração/fisiopatologia , Reflexo/fisiologia , Agonistas do Receptor de Serotonina/farmacologia , Animais , Eletromiografia , Potenciais Evocados/fisiologia , Masculino , Movimento/fisiologia , Piperazinas/farmacologia , Piridinas/farmacologia , Ratos , Ratos Wistar , Receptores de Serotonina/efeitos dos fármacos , Receptores 5-HT1 de SerotoninaRESUMO
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.
Assuntos
Área Pré-Óptica/fisiologia , Saciação/fisiologia , Comportamento Sexual Animal/fisiologia , Animais , Mapeamento Encefálico , Copulação/fisiologia , Ejaculação/fisiologia , Hipotálamo Anterior/fisiologia , Masculino , Inibição Neural/fisiologia , Ratos , Ratos WistarRESUMO
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.
Assuntos
Analgésicos Opioides/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Morfina/farmacologia , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Medula Espinal/efeitos dos fármacos , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Dependência de Morfina/fisiopatologia , Prazosina/farmacologia , Ratos , Ratos Wistar , Fatores Sexuais , Medula Espinal/patologiaRESUMO
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.
Assuntos
Copulação/fisiologia , Ejaculação/fisiologia , Desempenho Psicomotor/fisiologia , Animais , Eletromiografia , Masculino , Ratos , Ratos Wistar , Medula Espinal/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Vértebras Torácicas/lesõesRESUMO
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.
Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Dopamina/fisiologia , Resposta de Saciedade/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Ioimbina/farmacologia , Animais , Apomorfina/farmacologia , Copulação/efeitos dos fármacos , Copulação/fisiologia , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Ejaculação/efeitos dos fármacos , Ejaculação/fisiologia , Feminino , Haloperidol/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Resposta de Saciedade/fisiologia , Comportamento Sexual Animal/fisiologia , CaminhadaRESUMO
Previous reports have shown that intrabrain administration of progesterone (P) ring A-reduced metabolites into the medial preoptic area (MPOA) and ventromedial hypothalamus (VMH) induces facilitation of female sexual behavior in ovariectomized (ovx) rats pretreated with estrogen. Present studies were designed to explore the possibility that ring-A reduced progesterone metabolites might play a role in controlling the duration of estrous behavior. To this aim ovariectomized (ovx) Sprague Dawley rats implanted with guide cannulae directed towards the VMH or the MPOA were submitted to a systemic hormonal treatment to provoke P-induced sequential inhibition (estradiol benzoate (EB) at time O + P at 44 h + P at 68 h). The second dose of P was administered simultaneously with the i.c. implantation of one of the following P metabolites: 3 beta-hydroxy-5 beta-pregnan-20-one (5 beta,3 alpha P), 3 alpha-hydroxy-5 beta-pregnan-20-one (5 beta,3 alpha P) or 3 beta-hydroxy-5 beta- pregnan-20-one (5 alpha,3 beta P) into the MPOA or VMH. Lordosis behavior was evaluated by the lordosis quotient (LQ = number of lordosis/10 male mount x 100) and by the percentage of responding subjects. Results show that 5 beta,3 beta P implanted into the VMH or MPOA counteracted the sequential inhibitory effect induced by systemic administration of P.5 alpha,3 beta P was also able to counteract sequential inhibition, but with less potency and only in the VMFI. Results showed that P-induced sequential inhibition can be counteracted by intrabrain administration of ring-A reduced progestins in both the VMH and MPOA. Data are discussed in terms of a putative physiological role of naturally occurring P metabolites in P-mediated female sexual behavior expression.