Supraspinal site of action for the inhibition of ejaculatory reflex by dapoxetine.
OBJECTIVE
The aim of the study was to determine whether dapoxetine, a short-acting selective serotonin reuptake inhibitor, acts at the spinal or supraspinal level to inhibit the ejaculatory reflex.


METHODS
The pudendal motoneuron reflex discharges (PMRDs) model was used as an experimental paradigm of the ejaculatory expulsion reflex in anaesthetised male rats. A spinal site of action was evaluated by testing the effect of intrathecal delivery of dapoxetine on PMRDs elicited by electric stimulation of the dorsal nerves of the penis (DNP). A supraspinal site of action was evaluated by testing the effect of intravenous administration of dapoxetine on DNP-induced PMRDs in rats with chemical bilateral lesion of the lateral paragigantocellular nucleus (LPGi).


RESULTS
Compared with control (NaCl 0.9%, intrathecally), intrathecal injection of dapoxetine (1 and 80 microg) significantly increased amplitude of DNP-elicited PMRDs in a similar fashion than serotonin (5-HT; 10 and 100 microg, intrathecally). In rats having received bilaterally NaCl 0.9% into LPGi, intravenous treatment with dapoxetine (3mg/kg) induced significant delay in PMRD latency and decrease in PMRD amplitude compared with pretreatment values. These effects were abolished in rats having received bilaterally kainic acid into LPGi 1 d before testing.


CONCLUSIONS
The present study showed that dapoxetine inhibits ejaculatory expulsion reflex by acting at a supraspinal level with LPGi as a necessary brain structure for this effect.
Clément
Pierre
P
Pelvipharm Laboratories, CNRS, Gif-sur-Yvette, France.
Bernabé
Jacques
J
Gengo
Peter
P
Denys
Pierre
P
Laurin
Miguel
M
Alexandre
Laurent
L
Giuliano
François
F
D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage* / Q000494:pharmacology; D004542:Ejaculation / Q000187:drug effects*; D004558:Electric Stimulation; D007278:Injections, Spinal; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage* / Q000494:pharmacology; D010413:Penis / Q000187:drug effects* / Q000294:innervation*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects* / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology
D001596:Benzylamines; D009281:Naphthalenes; D017367:Selective Serotonin Reuptake Inhibitors; C080598:dapoxetine