Increased Ejaculation Latency Research Articles

Silencing and stimulating the medial amygdala impairs ejaculation but not sexual incentive motivation in male rats

The medial amygdala (MeA) is a sexually dimorphic brain region that integrates sensory information and hormonal signaling, and is involved in the regulation of social behaviors. Lesion studies have shown a role for the MeA in copulation, most prominently in the promotion of ejaculation. The role of the MeA in sexual motivation, but also in temporal patterning of copulation, has not been extensively studied in rats. Here, we investigated the effect of chemogenetic inhibition and stimulation of the MeA on sexual incentive motivation and copulation in sexually experienced male rats. AAV5-CaMKIIa viral vectors coding for Gi, Gq, or no DREADDs (sham) were bilaterally infused into the MeA. Rats were assessed in the sexual incentive motivation test and copulation test upon systemic clozapine N-oxide (CNO) or vehicle administration. We report that MeA stimulation and inhibition did not affect sexual incentive motivation. Moreover, both stimulation and inhibition of the MeA decreased the number of ejaculations in a 30 min copulation test and increased ejaculation latency and the number of mounts and intromissions preceding ejaculation, while leaving the temporal pattern of copulation intact. These results indicate that the MeA may be involved in the processing of sensory feedback required to reach ejaculation threshold. The convergence of the behavioral effects of stimulating as well as inhibiting the MeA may reflect opposing behavioral control of specific neuronal populations within the MeA.

Phytochemical and aphrodisiac studies of ethanol root extract of <i>Rauwolfia vomitoria</i> Afzel (Apocynaceae)

The root of Rauwolfia vomitoria (Afzel) is known for its anti-hypertensive, psychoactive properties and aphrodisiac potentials. This research work was aimed at studying the phytochemical constituents and aphrodisiac activities of the crude ethanol extract and its fractions. The root material was macerated for 72 h and the dried ethanol extract (EE) partitioned successively to obtain dichloromethane (DCM), ethyl acetate (EA), butanol (BuOH) and aqueous (AQ) fractions. The LD50 was determined using Miller and Tainter method. The aphrodisiac potential of the crude extract and these factions were evaluated using adult albino mature male rats. The crude ethanol extract was subjected to phytochemical screening. The median lethal dose (LD50) was determined to be 250±15.15mg/kg body weight. The result of phytochemical screening indicated the presence of alkaloids, saponins, cardiac glycosides, flavonoids, tannins and terpenoids. The extract and the fractions decreased mount latency, intromission latency, post ejaculation interval and increased ejaculation latency, mount frequency, erection frequency and penile erection. These effects were statistically significant (p<0.05, p<0.01, p<0.001) relative to control (normal saline). These findings authenticate the use of the root of Rauwolfia vomitoria as aphrodisiac agent.Keywords: Rauwolfia vomitoria; Aphrodisiac; Sexual dysfunction; Intromission; Mount latency

Spontaneous ejaculation with the use of noradrenergic reuptake inhibitors

The Netherlands Pharmacovigilance Centre Lareb maintainsthe spontaneous adverse drug reaction (ADR) reportingsystem in the Netherlands. The primary aim of this systemis to detect ADRs that were not identified prior to drugmarketing [1]. Physicians, pharmacists, and patients canreport suspected ADRs to the pharmacovigilance centre.We describe three case reports of spontaneous ejaculation,without sexual arousal, after micturition associated with theuse the noradrenergic reuptake inhibitors methylphenidate,atomoxetine, and venlafaxine reported by Lareb betweenJanuary 1996 and December 2011.Thefirstreport,fromapsychiatrist.concernsa40-year-oldman who received atomoxetine. After 3 weeks, the patientdeveloped spontaneous ejaculations following micturitionurgency up to eight times a day without sexual arousal. Thepatientrecoveredafterwithdrawalofatomoxetine.Thepatientpreviously used dexamphetamine, which also gave spontane-ous ejaculations. He recovered upon cessation of dexamphet-amine. Concomitant medication is not reported.The second report, from a consumer, concerns a 25-year-old man who experienced spontaneous ejaculation withoutsexual arousal following testicular pain after micturitionwith the use of methylphenidate. The use of concomitantmedication was not reported. Past drug therapy includedatomoxetine, which also gave spontaneous ejaculations fol-lowing micturition.After 2years, thepatientuses mainlythelong-acting variant of methylphenidate (Concerta®) andsometimes the shorter-acting variant of methylphenidate(Ritalin®). Although spontaneous ejaculations are still pres-ent, they are less frequent with this drug regimen.The third report, from a psychiatrist, concerns a 60-year-old man who experienced spontaneous ejaculations withoutsexual arousal one to two times a week within a day aftercommencing venlafaxine for depression. The ADR wors-ened after a dose increase from 225 to 375 mg. The outcomeof this report is unknown.In the literature, there are two case reports of spontaneousejaculation with sexual arousal with the use of reboxetine.Both patients recovered within 2 weeks of reboxetinewithdrawal [2, 3]. Case reports concerning spontaneousejaculation without sexual arousal with the use of othernoradrenergic reuptake inhibitors were described with theuse of milnacipran [4], zotepine [5], and nefazodone [6].Spontaneous ejaculation occurred after micturition [6] anddefecation [4], with a frequency varying from once per 2 or3weeks[4] to several [5] to seven times daily [6]. Allpatients recovered after drug withdrawal [4–6].The exact mechanism of spontaneous ejaculation is un-known. Ejaculation is controlled by both the sympathic andparasympathic system and consists of an emission and expul-sion phase [3]. Ejaculation latency time is regulated by thesympathic system. Hypothetically, by reducing ejaculatory la-tency time, spontaneous ejaculation can occur [3]. Adrenergicdrugs are sometimes used as treatment for delayed ejaculation[3].Inrats,ejaculationwasinducedbysystemicadministrationofamphetamine[7].Also,stimulationofnoradrenaline(rebox-etine [2], milnacipran [4]), and 5-hydroxytryptamine (5-HT2)antagonists (nefazodone) [6] could lead to decreased ejacula-tion latency time. On the other hand, selective serotonin reup-take inhibitors (SSRIs) [3, 4] and 5-HT1a antagonists couldlead to increased ejaculation latency time [2, 3].

Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility

Sibutramine is an inhibitor of norepinephrine and 5-HT reuptake largely used in the management of obesity. Although a fairly safe drug, postmarketing adverse effects of sibutramine were reported including abnormal ejaculation in men. This study investigates the effects of sibutramine on ejaculation and vas deferens and seminal vesicle contractility. Adult male rats received sibutramine (5; 20; or 50 mg kg − 1 , ip) and after 60 min were exposed to receptive females for determination of ejaculation parameters. The vasa deferentia and seminal vesicles of untreated rats were mounted in isolated organ baths for recording of isometric contractions and HEK293 cells loaded with fluorescent calcium indicator were used to measure intracellular Ca 2+ transients. Sibutramine 5 and 20 mg kg − 1 reduced ejaculation latency whereas 50 mg kg − 1 increased ejaculation latency. Sibutramine 3 to 30 μM greatly increased the sensitivity of the seminal vesicle and vas deferens to norepinephrine, but at concentrations higher than 10 μM there were striking depressions of maximal contractions induced by norepinephrine, carbachol and CaCl 2. In HEK293 cells, sibutramine 10 to 100 μM inhibited intracellular Ca 2+ transients induced by carbachol. Depending on the doses, sibutramine either facilitates or inhibits ejaculation. Apart from its actions in the central nervous system, facilitation of ejaculation may result from augmented sensitivity of smooth muscles to norepinephrine while reductions of intracellular Ca 2+ may be involved in the delayed ejaculation observed with high doses of sibutramine.

Sexual Dysfunction in Men Who Abuse Illicit Drugs: A Preliminary Report

Despite being seen as aphrodisiacs, illicit drugs are reported to have detrimental effects on male sexual function but most studies have been based on small case numbers with ambiguous results. To assess the impact of illicit drugs abuse on male sexual function. International Index of Erectile Function (IIEF) and global assessment questions. Illicit drug abusers in a Drug Abstention and Treatment Center were recruited to complete the questionnaires and their data were compared with an age-matched control. The abusers (N = 701, mean age 33.8 years) had a lower mean IIEF score in each domain than that of the controls (N = 196, mean age 35.4 years). Heroin, amphetamine, and MDMA ("Ecstasy") were the leading drugs used. Erectile dysfunction (ED) was reported in 36.4% of the abusers and the odds ratio of having ED (compared with the controls) in mono-users of heroin, amphetamine, and MDMA was 4.8 (P < 0.05), 3.2 (P < 0.05), and 1.4 (P > 0.05), respectively. Of the abusers, 38.6% reported to have decreased sexual desire with illicit drug use, more often seen in the heroin mono-users (46.7%), and 18.4% reported to have enhanced sexual desire, more often seen in the amphetamine mono-users (22.6%). Mean IIEF sexual desire domain score of the abusers was lower than that of the control, even for those who reported to have enhanced sexual desire. Increased and decreased ejaculation latency affected by illicit drugs was reported in 49.9 and 14.3%, respectively, of the abusers, showing no significant difference among the mono-users of three different drugs. Illicit drug male abusers were prone to have ED, decreased sexual desire, and increased ejaculation latency. ED and decreased sexual desire were most commonly seen in heroin, followed by amphetamine and MDMA mono-users, while increased ejaculation latency occurred commonly in all of the abusers.

Influence of exogenous GnRH on sexual behavior and frozen/thawed semen viability in stallions during the non-breeding season

Twelve fertile stallions were divided into two groups, either receiving gonadotropin-releasing hormone (GnRH) ( n=6) or Placebo ( n=6). Based on the history of frozen/thawed semen characteristics three stallions within each group were assigned as being “good freezers” [GnRH (+); Placebo (+)] and three stallions were assigned as being “poor freezers” [GnRH (−); Placebo (−)]. The study was performed as a “blinded” investigation and stallions were treated twice daily by an intramuscular injection of 1 ml GnRH (Buserelin ®, 50 μg) or Placebo. The experiment was divided into three time periods. Period A (pre-treatment) was performed between 16 November and 20 December; Period B (treatment) was performed during 6 weeks between 21 December and 31 January; and Period C (post-treatment) was performed between 1 February and 12 February. Semen was collected every Monday, Wednesday, Friday, and analysed for motion characteristics by the use of a computerized semen analyser, and sperm morphology immediately after collection. The spermatozoa were cryopreserved, stored in liquid nitrogen, and evaluated for motility (computer assisted semen analysis), membrane integrity (carboxyfluoresceine diacetate (CFDA) combined with propidium-iodide (PI), CFDA/PI), viability and sperm morphology (Eosine–Nigrosine, EN), and osmotic reactivity (hypo-osmotic swelling test, HOS) following thawing in a water bath. The viability of spermatozoa was expressed as the difference between pre-freeze and post-thaw values. A libido score of 1–4, the number of mounts on the phantom before ejaculation, and ejaculation latency were used to evaluate the stallions sexual behavior. Effect of treatment was analysed by comparing time intervals within groups as well as comparing groups within time intervals using SAS statistics software. GnRH treatment decreased the number of mounts before ejaculation (GnRH (total): 2.5±1.14 versus 1.8±1.06, P<0.05), and shortened ejaculation latency. Cessation of treatment increased ejaculation latency in the GnRH group (4.7±4.98 min versus 7.2±7.88 min, P<0.05). With the exception of libido score all parameters of sexual behavior were superior in the GnRH (+) group compared to the Placebo (−) group during the treatment period ( P<0.05). GnRH administration increased progressive motility (GnRH (+): 30.7±10.74% versus 38.4±15.1%, P<0.05; GnRH (total): 24.9±11.80% versus 31.9±14.68%, P<0.05), membrane intact spermatozoa CFDA/PI (GnRH (−): 16.8±7.17% versus 26.2±7.02%, P<0.05; GnRH (total): 23.1±12.33% versus 29.5±10.77%, P<0.05) and HOS positive spermatozoa (GnRH (+): 33.2±11.29% versus 42.2±10.36%, P<0.05; GnRH (total): 32.9±10.23% versus 40.1±10.30%, P<0.05) of frozen/thawed spermatozoa. Following cessation of treatment, the viability of frozen/thawed spermatozoa decreased. GnRH treated stallions had lower losses of live stained spermatozoa (EN) compared to the Placebo group (GnRH (total): 17.6±4.77 versus Placebo (total): 27.2±5.44, P<0.05). This was particularly observed in the “poor freezer” group (GnRH (−): 16.6±4.35 versus Placebo (−): 31.3±5.87; P<0.05). In conclusion, exogenous GnRH was shown to improve sexual behavior and increase the quality of frozen/thawed spermatozoa in fertile stallions during the non-breeding season. Nevertheless, it seems that, although significance was achieved relative to improvement to post-thaw sperm quality, that the “real” change in sperm quality seems negligible in fertile stallions. The mechanism of GnRH effect was not determined but this study may support the possibility of a direct gonadal or epididymal effect of exogenous GnRH in the stallion.

Evidence for an involvement of 5-HT1B receptors in the inhibition of male rat ejaculatory behavior produced by 5-HTP.

The administration of the 5-hydroxytryptamine (5-HT) precursor 5-hydroxytryptophan (5-HTP) (25 mg/kg i.p.), in combination with an inhibitor of peripheral 5-HTP decarboxylase, produced a dose-dependent increase in the ejaculation latency of male rats, and this effect was enhanced by additional treatment with the 5-HT1 receptor antagonist (-)-pindolol (2 mg/kg s.c.). The 5-HT2A/C receptor agonist (+/-) 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.125-0.5 mg/kg s.c.) did not by itself affect male ejaculatory behavior, but additional treatment with (-)-pindolol (2 mg/kg s.c.) produced a dose-dependent decrease in number of ejaculating animals. The increased ejaculation latency produced by 5-HTP was fully antagonized by treatment with the 5-HT1B receptor antagonist isamoltane (4 mg/kg s.c.), but not by ritanserin (2 mg/kg s.c.) treatment. The selective 5-HT1A receptor antagonist WAY-100635 (0.15 mg/kg s.c.) enhanced the inhibitory actions of 5-HTP on the male rat ejaculatory behavior, and this dose of WAY-100635 fully antagonized 8-OH-DPAT-induced facilitation (0.25 mg/kg s.c.) of the ejaculatory behavior. WAY-100635 (0.04-0.60 mg/kg s.c.) did not, by itself, significantly affect male rat sexual behavior. Taken together, the results suggest an inhibitory role for postsynaptic 5-HT1B receptors in the effects produced by 5-HTP on male rat ejaculatory behavior. Furthermore, 5-HTP-induced inhibition of male rat ejaculatory behavior is partially controlled by stimulation of inhibitory 5-HT1A autoreceptors, since the effects of 5-HTP were accentuated by treatment with (-)-pindolol, as well as by the more selective 5-HT1A receptor antagonist WAY-100635.

The Selective Serotonin Reuptake Inhibitor Fluoxetine Reduces Sexual Motivation in Male Rats

VEGA MATUSZCZYK, J., K. LARSSON AND E. ERIKSSON. The selective serotonin reuptake inhibitor fluoxetine reduces sexual motivation in male rats. PHARMACOL BIOCHEM BEHAV 60(2) 527–532, 1998.—A male rat put in an open-field arena in which it is free to spend time in the vicinity of—but not in contact with—an estrous female, or in the vicinity of a male, usually spends more time with the female than with the male or elsewhere. Tentatively, the percentage of time spent in the vicinity of the female in this paradigm may be regarded as a measure of sexual motivation. In humans, treatment with selective serotonin reuptake inhibitors (SSRIs) may cause reduced libido. To investigate to what extent serotonin reuptake inhibition influences sexual motivation also in rats, we have tested the effect of subchronic treatment with fluoxetine on the behavior in the sexual motivation test described above; in addition, the effect of fluoxetine on male copulatory behavior was studied. Fluoxetine significantly reduced sexual motivation at subchronic but not at acute administration; moreover, fluoxetine-treated rats displayed an increased ejaculation latency. It is concluded that humans and rats respond similarly to the SSRI fluoxetine with respect to various aspects of sexual behavior.

Amantadine stimulates sexual behavior in male rats

The effects of amantadine on sexual behavior, penile erection, and seminal emission of male rats was studied. Amantadine significantly decreased latency of mounts in all doses (1.25 to 50 mg/kg), and decreased the number of mounts and intromission latency at the highest doses used. The lowest dose of amantadine significantly increased ejaculation latency and intromission frequency, while higher doses significantly reduced it, which indicates a biphasic response of the drug. Additionally, seminal emission, erections, and genital grooming were significantly induced by amantadine. Amantadine-induced seminal emissions were impaired by spinal cord transection, which suggests the involvement of supraspinal structures in the drug action. Haloperidol and atropine sulphate significantly reduced seminal emissions and penile erections induced by amantadine. These results demonstrate that amantadine stimulates sexual behavior and genital reflexes in male rats and suggest a facilitatory effect of the drug that probably involves different mechanisms of action.

Yohimbine and naloxone: Effects on male rat sexual behavior

We evaluated the effects of yohimbine (2 mg/kg) and naloxone (5 mg/kg), separately and in combination, on copulatory behavior in male rats. In Experiment 1, yohimbine evinced decrements in intromission frequency, ejaculation latency, and copulatory efficiency, whereas naloxone administration was followed by an increased ejaculation latency, and the combination of yohimbine plus naloxone was without effect. In Experiment 2, yohimbine evinced decreases in intromission frequency, ejaculation latency, copulatory efficiency in the first, but not subsequent, copulatory series, as well as a decreased latency to sexual exhaustion. Further, treatment with yohimbine alone, naloxone alone, or yohimbine plus naloxone was followed by a reduction in the number of ejaculations prior to sexual exhaustion. Thus, at the doses tested, no synergistic effects were observed for the combination of yohimbine plus naloxone.