Effects of SSRIs on Sexual Function

High or repeated doses of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy') produce long-lasting deficits in several markers of serotonin (5-HT) system integrity and also alter behavioral function. However, it is not yet clear whether MDMA-induced serotonergic neurotoxicity is responsible for these behavioral changes or whether other mechanisms are involved. The present experiment tested the hypothesis that blocking serotonergic neurotoxicity by pretreatment with the selective 5-HT reuptake inhibitor citalopram will also prevent the behavioral and physiological consequences of an MDMA binge administration. Male, SpragueDawley rats (N ¼ 67) received MDMA (4 Â 10 mg/kg) with or without citalopram (10 mg/kg) pretreatment. Core temperature, ejaculatory response, and body weight were monitored during and immediately following drug treatments. A battery of tests assessing motor, cognitive, exploratory, anxiety, and social behaviors was completed during a 10-week period following MDMA administration. Brain tissue was collected at 1 and 10 weeks after drug treatments for measurement of regional 5-HT transporter binding and (for the 1-week samples) 5-HT and 5-HIAA concentrations. Citalopram pretreatment blocked MDMA-related reductions in aggressive and exploratory behavior measured in the social interaction and hole-board tests respectively. Such pretreatment also had the expected protective effect against MDMA-induced 5-HT neurotoxicity at 1 week following the binge. In contrast, citalopram did not prevent most of the acute effects of MDMA (eg hyperthermia and weight loss), nor did it block the decreased motor activity seen in the binge-treated animals 1 day after dosing. These results suggest that some of the behavioral and physiological consequences of a high-dose MDMA regimen in rats are mediated by mechanisms other than the drug's effects on the serotonergic system. Elucidation of these mechanisms requires further study of the influence of MDMA on other neurotransmitter systems.

Section: Discussionmentioning

confidence: 98%

Section: Physiological Measuresmentioning

confidence: 99%

Dissociation of the Neurochemical and Behavioral Toxicology of MDMA (‘Ecstasy’) by Citalopram

Piper

Fraiman

Owens

et al. 2007

“…A number of previous investigations have discussed the relative effects of serotonergic agents, such as SSRIs, on the different aspects of sexual well-being (Kennedy et al, 2000;Montejo et al, 2001;Rosen et al, 1999). Notably, the most clinically significant effects seem to be on arousal in women and orgasm in men (Clayton et al, May 2003).…”

Section: Discussionmentioning

confidence: 99%

Serotonin 2A −1438 G/A and G-Protein Beta3 Subunit C825T Polymorphisms in Patients with Depression and SSRI-Associated Sexual Side-Effects

Bishop

Moline

Ellingrod

et al. 2006

The occurrence of sexual side-effects from antidepressants is thought to be mediated through serotonin 2A (5HT2A) receptors. It is currently unknown if functional polymorphisms in the 5HT2A receptor or its G-protein second messenger complex are related to sexual dysfunction in patients taking an selective serotonin reuptake inhibitor (SSRI) for depression. The purpose of this study was to determine the relationship of the 5HT2A À1438 G/A and GNB3 C825T single nucleotide polymorphisms with overall sexual well-being and individual components of sexual health as measured by the Changes in Sexual Functioning Questionnaire (CSFQ). We evaluated 89 outpatients (18-40 years of age) at low risk for other causes of sexual dysfunction who were being treated for depression with an SSRI and did not have sexual difficulties before taking the antidepressant. Outcome measures were stratified by 5HT2A and GNB3 genotypes. After controlling for age, gender, anxiety scale scores, and depression scale scores, persons with a GG genotype of the 5HT2A À1438 single nucleotide polymorphisms (SNP) were significantly more likely to be categorized as having sexual dysfunction than persons with a GA or AA genotype (OR ¼ 3.6; 95% CI 1.03, 12.6; p ¼ 0.046). Furthermore, the 5HT2A À1438 GG genotype was a significant predictor of lower arousal scores (p ¼ 0.022) after accounting for other measures. There was no significant relationship between any outcome measure and GNB3 genotype.

“…There is evidence to suggest that inhibitors of phosphodiesterase 5 (PDE-5), such as sildenafil and zaprinast, can significantly improve SSRI-induced sexual dysfunction in women (Fava et al, 1998;Rosen et al, 1999). Women taking SSRIs who received 50 or 100 mg of sildenafil self-report improved sexual function (Ashton, 1999;Schaller and Behar, 1999;Shen et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Zaprinast, a Phosphodiesterase 5 Inhibitor, Overcomes Sexual Dysfunction Produced by Fluoxetine, a Selective Serotonin Reuptake Inhibitor in Hamsters

Frye

Rhodes

2003

A high incidence of sexual dysfunction among women is reported in the clinical literature. Little experimental investigation has been initiated on the ability of phosphodiesterase (PDE) inhibitors to overcome deficits in sexual functioning because of selective serotonin reuptake inhibitors (SSRIs). The effects of fluoxetine, an SSRI, and zaprinast, a PDE-5 inhibitor, on the lateral displacement response (used as a measure of sensitivity to reproductively relevant stimuli) of hamsters in behavioral estrus were investigated. In Experiment 1, hamsters that were maximally sensitive to reproductively relevant stimuli because they were at the peak of behavioral estrus were administered fluoxetine (10 mg/kg, i.p.); they had significantly decreased lateral displacement responses compared to vehicleadministered hamsters. In Experiment 2, hamsters that were relatively less sensitive to sexual stimuli because they were at the termination of behavioral estrus were administered zaprinast (3 mg/kg; i.p.); they had significantly enhanced lateral displacement responses compared to responses seen following vehicle administration. In Experiment 3, fluoxetine-induced deficits in the lateral displacement of hamsters at the peak of behavioral estrus were overcome by the coadministration of zaprinast. These data confirm previous findings that sexual dysfunction can be induced by SSRIs and extend the current knowledge to suggest that administration of a PDE-5 inhibitor can override SSRI-induced deficits in sexual functioning.