Moderate Role of Oxytocin in the Pro-Ejaculatory Effect of the 5-HT1A Receptor Agonist 8-OH-DPAT

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The neurobiological control of ejaculation is not completely understood. Both serotonin (5-HT) and oxytocin (OXT) play a role in the control of male sexual parameters, putatively via overlapping neuronal networks.


The aim of this study was to determine whether activation of 5-HT1A receptors (5-HT1ARs) reduces the ejaculatory threshold via the direct activation of (OXT) neurons in the paraventricular hypothalamic nucleus (PVN).


In experiment 1, male rats received acute bilateral infusions of the selective 5-HT1AR antagonist WAY-100635 (1 and 10 μg) or vehicle into the PVN, followed by acute subcutaneous (SC) injection of the potent 5-HT1AR agonist 8-OH-DPAT (0.4 mg/kg) or saline. In experiment 2, male rats received acute bilateral infusions of 8-OH-DPAT (1 and 10 μg) or vehicle into the PVN. In experiment 3, male rats received acute intracerebroventricular (ICV) infusion of a selective OXT receptor antagonist (OXTR-A, 75 and 750 ng) followed by acute SC injection of 8-OH-DPAT (0.4 mg/kg) or saline. The effects of these drug treatments on sexual behavior were measured.

Main Outcome Measures.

Copulation latency, ejaculation latency, mount and intromission frequency, and ejaculation frequency of sexually experienced adult male Wistar rats during 30-minute sexual behavior tests with a receptive female were the main outcome measures.


Male sexual behavior was not affected by intra-PVN infusion of WAY-100635 or 8-OH-DPAT, or by ICV infusion of OXTR-A alone. However, the facilitation of ejaculation (reduced mount and intromission frequency and ejaculation latency) induced by systemic 8-OH-DPAT could be attenuated by either intra-PVN infusion of WAY-100635 or by ICV infusion of OXTR-A.


Activation of OXT neurons plays a moderate role in the pro-ejaculatory effects of systemic 8-OH-DPAT, but extracellular 5-HT levels may influence the strength of the effects. de Jong TR and Neumann ID. Moderate role of oxytocin in the pro-ejaculatory effect of the 5-HT1A receptor agonist 8-OH-DPAT. J Sex Med 2015;12:17–28.

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