Supraspinal site of action for the inhibition of ejaculatory reflex by dapoxetine
Abstract
OBJECTIVES: 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…
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