Pierre Clément

Ejaculation induced by I.C.V. injection of the preferential dopamine D3 receptor agonist 7-hydroxy-2-(Di-N-propylamino)tetralin in anesthetized rats

In addition to serotonin, dopamine within the CNS is known to play a primary role in the control of ejaculation. However, whether D(2) and/or D(3) dopamine receptor subtypes mediate this effect is still unclear. In order to clarify this issue, a pharmacological competitive study using the preferential D(3) agonist 7-hydroxy-2-(di-N-propylamino)tetralin (7-OH-DPAT) alone or in combination with competitive nonpreferential or preferential D(2) and D(3) antagonists delivered intracerebroventricularly (i.c.v.) was undertaken in anesthetized rats. Urethane-anesthetized male rats were implanted into the cerebral ventricle with a cannula for i.c.v. injections, and recording electrodes were placed within the bulbospongiosus (BS) muscle to monitor BS muscle contractions, which were used as a marker for the expulsion phase of ejaculation. Following i.c.v. injection, 7-OH-DPAT induced ejaculation and rhythmic BS muscle contractions. Co-injected i.c.v. with 7-OH-DPAT, the nonselective D(2)/D(3) antagonist (raclopride), and the preferential D(3) antagonist (S(-)-N[n-butyl-2-pyrrolidinyl)methyl]-1-methoxy-4-cyanonaphtalene-2-carboxamide; nafadotride) but not the preferential D(2) antagonist ((+/-)-3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole; L 741,626) inhibited the occurrence of ejaculation and BS muscle contractions. These results suggest that i.c.v. delivery of 7-OH-DPAT does represent a pertinent model to investigate the physio-pharmacology of ejaculation. It is inferred that targeting brain D(3) receptors may provide a therapeutic approach for treating ejaculatory disorders in humans.

Microinjection of the preferential dopamine receptor D3 agonist 7-hydroxy-N,N-di-N-propylaminotetralin hydrobromide into the hypothalamic medial preoptic area induced ejaculation in anesthetized rats

The pivotal role of the medial preoptic area (MPOA) of the hypothalamus in the dopaminergic cerebral control of ejaculation has been investigated for years; nevertheless the function of different dopamine receptors subclasses and their exact interrelations merit additional research. One hundred nanograms of a preferential D(3) agonist 7-OH-DPAT (7-hydroxy-N,N-di-n-propylaminotetralin hydrobromide) was microinjected unilaterally into the MPOA of male rats anesthetized with urethane. An ejaculation-related response (bulbospongiosus muscles rhythmic contractions and/or seminal vesicle pressure increases and/or expulsion of a semen plug) was observed in 8 of 10 rats devoid of sexual stimuli, while a similar response was observed in only one rat administered with 10 ng of 7-OH-DPAT. The effect of 7-OH-DPAT 100 ng was mostly abolished by simultaneous MPOA microinjection of 300 ng of a preferential D(3) antagonist N-[(n-butyl-2-pyrrolidinyl) methyl]-1-methoxy-4-cyanonaphthalene-2-carboxamide tartrate (nafadotride). Our results support the hypothesis that supraspinal command of ejaculation is mediated by D(2)-like receptors, probably by D(3) receptors, in the MPOA, and draw attention to the idea of these receptors serving as a promising target for pharmacological treatment of human ejaculatory disorders.

Comparison between tamsulosin and alfuzosin on the expulsion phase of ejaculation in rats

To investigate the effects of acute intravenous (i.v.) delivery of tamsulosin and alfuzosin on the contractions of bulbospongiosus muscles (BS) induced by central delivery of a serotonin agonist, 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT), in anaesthetized rats, as an experimental model of the expulsion phase of ejaculation.

Melanotan-II: Investigation of the inducer and facilitator effects on penile erection in anaesthetized rat.

The effects of melanotan-II, a non-specific agonist of melanocortin receptors, on erection and its possible sites of action were investigated in anesthetized rats. Delivered i.v. (0.1, 0.3 and 1 mg/kg) or within the paraventricular nucleus of the hypothalamus (0.1 and 1 microg), melanotan-II exerted a dose-dependent inducer activity on erection by eliciting erectile events and shortening latency of the first erectile event to occur. Erectile events were of higher amplitude in rats treated with melanotan-II i.t. (0.2 microg) delivered at the L6-S1 level than in animals treated with the vehicle i.t. delivered. Erectile responses elicited by cavernous nerve stimulation were increased after i.v. melanotan-II (1 mg/kg), thereby exerting facilitator effect on erection. In contrast, melanotan-II injected within the corpus cavernosum (1 microg) did not display any facilitator activity. To investigate the neural pathways involved in the facilitator effect of melanotan-II, we performed acute spinalization (T8 level) and differential selective nerve transections. Neither spinalization nor bilateral transection of pelvic nerves or dorsal penile nerves impaired facilitator activity of i.v. melanotan-II (1 mg/kg). Conversely, the facilitator effect of melanotan-II was abolished after acute removal of the lumbar paravertebral sympathetic chain. These results lead to the conclusion that central and peripheral melanocortin pathways are recruited by melanotan-II, depending on its route of delivery, to exert both inducer and facilitator activities on erection.

Seminal Plug Expulsion Induced by Electrical Stimulation of the Intermesenteric Nerve in Anesthetized Rats

Abstract Synchronized activation of autonomic and somatic divisions of the nervous system respectively destined to the seminal tract, including the bladder neck and the pelvi-perineal striated musculature, is necessary for anterograde ejaculation. We aimed at investigating the role of intermesenteric nerves (IMNs) in ejaculation in anesthetized rats. Electrical stimulation of intact IMNs and distal and proximal stumps of the sectioned IMN were tested in isoflurane-anesthetized male rats. Electrical stimulation of the intact IMN was also applied to rats with acute spinal transection at the T8 level. The effects of IMN electrical stimulation on emission and expulsion phases of ejaculation were evaluated by measuring seminal vesicle pressure (SVP) and bulbospongiosus (BS) muscle contractions, respectively. IMN electrical stimulation could induce SVP increase and rhythmic contractions of BS muscle concomitantly with expulsion of the seminal plug. When compared with intact IMN electrical stimulation, the occurrence of ejaculation and rhythmic BS muscle contractions, but not SVP increase, was reduced in response to electrical stimulation of the distal stump of the sectioned IMN. In comparison to intact IMN electrical stimulation, the occurrence of ejaculation and rhythmic BS muscle contractions was not significantly modified, whereas the increase in SVP was diminished when the proximal stump of the sectioned IMN was stimulated. Spinalization abolished ejaculation and rhythmic BS muscle contraction but did not impair SVP increase. It is concluded that both afferents conveyed by IMN and relaying supraspinally and efferents of IMN are involved in IMN electrical stimulation-induced ejaculation. We propose that the IMN electrical stimulation paradigm can be used to investigate physiological and pharmacologic aspects of ejaculation.

Assessment of Bedload Delivery from Tributaries: The Drôme River Case, France

This paper examines the potential to reverse bed degradation trends in the Dr6me River (southeast France), a prealpine gravel-bed stream, by assessing coarse sediment supply in tributary subbasins. Two approaches are developed. First, a Principal Component Analysis was performed on 24 subwatersheds to characterize the most productive ones. Second, fieldwork and aerial photographs provide detailed assessment for two mountain streams, one characterized by abundant bedload (the Esconavette Creek), the other characterized by 30 yr of inactivity (the Barnavette Creek). Active tributaries (with developed active gravel bars) have been discriminated according to variables describing watershed sediment storage and production potential. Variables describing human intervention on erosion and vegetation cover appear to exert secondary influences on geomorphic activity in a context of general geomorphic stabilization. Declining activity associates features such as bed incision, channel narrowing, and vegetation development in riparian buffer strips in the two mountain streams studied. They are more frequent on the Barnavette Creek, the inactivity of which is partly explained by smaller lateral inputs from valley-filling.