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SRIs + oxytocin: orgasm, tachyphalaxis, flatness??

Posted by desolationrower on May 13, 2009, at 16:12:36

No seriously ignore the orgasm stuff. Oxytocinergic desisitization - mightnt this have broader negative impact? i think its mentioned commonly for the prosocial effects of mdma.

Oxytocin Involvement in SSRI-Induced Delayed Ejaculation: A Review of Animal Studies
Trynke R. de Jong, PhD,* Jan G. Veening, PhD,*
,Berend Olivier, PhD,* , and Marcel D. Waldinger, MD, PhD* ,§

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) differ in the severity of induced ejaculation delay. Various studies indicate that oxytocin is involved in sexual behavior. AIM: To review and evaluate the involvement of oxytocin in SSRI-induced ejaculation delay. MAIN OUTCOME MEASURES: 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.

PMID: 17233773 [PubMed - indexed for MEDLINE


read the whole thing: http://faculty.ucr.edu/~saltzman/Trynke/Research_files/dejong07.pdf

Note: this seems to indicate the pathway goes the otherway, although it might be going both ways of course:

Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice.
Yoshida M, Takayanagi Y, Inoue K, Kimura T, Young LJ, Onaka T, Nishimori K.

Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai, Miyagi 981-8555, Japan.

The oxytocin receptor has been implicated in the regulation of reproductive physiology as well as social and emotional behaviors. The neurochemical mechanisms by which oxytocin receptor modulates social and emotional behavior remains elusive, in part because of a lack of sensitive and selective antibodies for cellular localization. To more precisely characterize oxytocin receptor-expressing neurons within the brain, we generated an oxytocin receptor-reporter mouse in which part of the oxytocin receptor gene was replaced with Venus cDNA (a variant of yellow fluorescent protein). Examination of the Venus expression revealed that, in the raphe nuclei, about one-half of tryptophan hydroxylase-immunoreactive neurons were positive for Venus, suggesting a potential role for oxytocin in the modulation of serotonin release. Oxytocin infusion facilitated serotonin release within the median raphe nucleus and reduced anxiety-related behavior. Infusion of a 5-HT(2A/2C) receptor antagonist blocked the anxiolytic effect of oxytocin, suggesting that oxytocin receptor activation in serotonergic neurons mediates the anxiolytic effects of oxytocin. This is the first demonstration that oxytocin may regulate serotonin release and exert anxiolytic effects via direct activation of oxytocin receptor expressed in serotonergic neurons of the raphe nuclei. These results also have important implications for psychiatric disorders such as autism and depression in which both the oxytocin and serotonin systems have been implicated.

-d/r

 

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