Oxytocin involvement in SSRI-induced delayed ejaculation: a review of animal studies.
BACKGROUND
Selective serotonin reuptake inhibitors (SSRIs) differ in the severity of induced ejaculation delay. Various studies indicate that oxytocin is involved in sexual behavior.


OBJECTIVE
To review and evaluate the involvement of oxytocin in SSRI-induced ejaculation delay.


METHODS
Oxytocine release, 5-hydroxytryptamine (5-HT) neurotransmission, and desensitization of 5-HT(1A) receptors.


METHODS
A review and critical analysis of animal studies investigating the interaction of serotonergic and oxytocinergic neurotransmission in relation to the ejaculation process.


RESULTS
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.


CONCLUSIONS
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.
de Jong
Trynke R
TR
Department of Psychopharmacology, Utrecht Institute of Pharmacological Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, the Netherlands.
Veening
Jan G
JG
Department of Psychopharmacology, Utrecht Institute of Pharmacological Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, the Netherlands;; Department of Anatomy, Radboud University Medical Center, Nijmegen, the Netherlands.
Olivier
Berend
B
Department of Psychopharmacology, Utrecht Institute of Pharmacological Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, the Netherlands;; Department of Psychiatry, Yale University Medical School, New Haven, CT, USA.
Waldinger
Marcel D
MD
Department of Psychopharmacology, Utrecht Institute of Pharmacological Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, the Netherlands;; Department of Psychiatry and Neurosexology, HagaHospital Leyenburg, The Hague, the Netherlands. Electronic address: md@waldinger.demon.nl.
D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004542:Ejaculation / Q000187:drug effects*; D007172:Erectile Dysfunction / Q000188:drug therapy*; D008297:Male; D010121:Oxytocin / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D012726:Sexual Behavior, Animal / Q000187:drug effects
D010121:Oxytocin; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors