Oxytocin Involvement in SSRI-Induced Delayed Ejaculation: A Review of Animal Studies

Abstract

Selective serotonin reuptake inhibitors (SSRIs) differ in the severity of induced ejaculation delay. Various studies indicate that oxytocin is involved in sexual behavior. To review and evaluate the involvement of oxytocin in SSRI-induced ejaculation delay. Oxytocine release, 5-hydroxytryptamine (5-HT) neurotransmission, and desensitization of 5-HT(1A) receptors. A review and critical analysis of animal studies investigating the interaction of serotonergic and oxytocinergic neurotransmission in relation to the ejaculation process. Although acute treatment with the SSRIs fluoxetine and paroxetine immediately causes increased serotonin levels, delayed ejaculation does not occur. The increased serotonin levels induce oxytocin release via activation of 5-HT(1A) receptors, and this might compensate for the inhibitory actions of serotonin on sexual behavior. Chronic treatment with fluoxetine and paroxetine desensitizes 5-HT(1A) receptors on oxytocin neurons, and that might in part determine the onset of delayed ejaculation. Desensitization of 5-HT(1A) receptors is less strong following chronic treatment with the SSRIs fluvoxamine or citalopram, which may attenuate the degree of delayed ejaculation. Preliminary data suggest that the severity of chronic SSRI treatment-induced delayed ejaculation and the differences between the various SSRIs in inducing ejaculation delay is related to gradual desensitization of 5-HT(1A) receptors on oxytocin neurons.