Brain oxytocin receptors mediate ejaculation elicited by 7-hydroxy-2-(di-N-propylamino) tetralin (7-OH-DPAT) in anaesthetized rats

Background and purpose: The involvement of the neuropeptide oxytocin in the control of male sexual responses is documented although its exact mechanisms of action, and especially the site(s) of action, are not fully delineated. In order to clarify this issue, we tested the effects of a peptide oxytocin antagonist delivered through different routes on sexual responses elicited, in anaesthetized male rats, by i.c.v. 7-hydroxy-2-(di-N-propylamino) tetralin (7-OH-DPAT), a dopamine agonist, preferentially active on D-3 receptors. Experimental approach: Seminal vesicle pressure (SVP) and bulbospongiosus muscle (BS) electromyograms were recorded as physiological markers of emission and expulsion phases of ejaculation respectively and intracavernosal pressure (ICP) was monitored as a physiological marker of erection. Key results: When injected i.v., the oxytocin antagonist did not impair 7-OH-DPAT-induced SVP and ICP responses while BS burst frequency was diminished. When delivered i.c.v., the oxytocin antagonist dose-dependently inhibited occurrence of 7-OH-DPAT-induced sexual responses. When delivered intrathecally (i.t.) at the level of the 6(th) lumbar (L6) segment, but not the 13(th) thoracic (T13) segment, the oxytocin antagonist reduced the duration of BS responses and the occurrence of ejaculation without impairing ICP responses. Conclusions and implications: Brain oxytocin receptors mediate male sexual responses elicited by i.c.v. 7-OH-DPAT in anaesthetized rats whereas L6 spinal oxytocin receptors only impair the occurrence of ejaculation. Peripheral oxytocin receptors are marginally involved in 7-OH-DPAT-induced sexual responses. These findings should be considered for the development of potential pharmacological treatment of premature ejaculation in man.