Effect of dapoxetine on ejaculatory performance and related brain neuronal activity in rapid ejaculator rats.
BACKGROUND
A brain network specifically activated when ejaculation occurs has been described in rats. Increasing serotonin (5-hydroxytryptamine [5-HT]) tone impairs ejaculation and chronic 5-HT selective serotonin reuptake inhibitors (SSRIs) are known to inhibit ejaculation. However, efficacy of acute treatment with SSRI varies from one compound to another. The SSRI dapoxetine has been reported to delay ejaculation when given on demand to men with premature ejaculation (PE), although the mechanism of action is unclear. Effects of acute SSRIs on activity of the brain ejaculation circuit in relation with ejaculation have never been examined.


OBJECTIVE
To test the effects of acute administration of the short half-life SSRI dapoxetine on ejaculatory performance and activity in brain ejaculation circuit in rapid ejaculator rats taken as PE model.


METHODS
Standard copulatory test was used to attribute one sexual category (sluggish, middle, or rapid) to male rats on the basis of their ejaculatory performance. Parameters of sexual, including ejaculatory, behavior, and Fos level of expression in discrete brain areas were assessed in the three sexual categories and in rapid category following acute oral treatment with dapoxetine.


METHODS
Ejaculation frequency (EF) and latency (EL) were measured as primary end points of ejaculatory behavior. Density of Fos-immunopositive cells in specific brain areas of brain stem, hypothalamus, and thalamus was determined as marker of neuronal activity.


RESULTS
EL and Fos level of expression in hypothalamic and thalamic structures were found related. Dapoxetine acute oral administration (300 mg/kg) to rapid ejaculator rats resulted in (i) diminution of ejaculatory performance (lengthened EL and decreased EF); and (ii) modulation of Fos level of expression in hypothalamic and thalamic nuclei of the brain ejaculatory circuit.


CONCLUSIONS
Acute treatment with dapoxetine, which reduced ejaculatory performance in rapid ejaculator rats, was also accompanied with changes in neuronal activity in components of the brain ejaculatory network.
Pelvipharm Laboratories, Orsay, France. p.clement@pelvipharm.com
Pierre
P
Clément
Miguel
M
Laurin
Sandrine
S
Compagnie
Patricia
P
Facchinetti
Jacques
J
Bernabé
Laurent
L
Alexandre
François
F
Giuliano
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004542:Ejaculation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D061686:Premature Ejaculation / Q000188:drug therapy*; D051381:Rats; D011913:Rats, Inbred BB; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012726:Sexual Behavior, Animal
D001596:Benzylamines; D009281:Naphthalenes; D017367:Selective Serotonin Reuptake Inhibitors; C080598:dapoxetine