PAROXETINE-INDUCED DOPAMINE DYSREGULATION: INSIGHTS INTO THE PATHOGENESIS OF POST-SSRI SEXUAL DYSFUNCTION (PSSD) (2025)
Abstract
Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used to treat mental health conditions but are linked to sexual dysfunction and libido issues. The underlying mechanisms remain unclear. This research explores the immediate and long-term effects of SSRI treatment, trying to mimic the post-SSRI sexual dysfunction (PSSD), where sexual side effects persist after stopping the medication. We investigated how the SSRI paroxetine affects dopamine levels and gene expression in the nucleus accumbens (NAc), a brain region involved in sexual motivation.
Adult male rats were treated with paroxetine for 14 days, and dopamine levels were analyzed in NAc 24 hours post-treatment and after a one-month suspension period. Dopamine concentrations were measured using mass spectrometry, while real-time PCR was employed to evaluate the expression of key genes involved in dopaminergic pathways, such as MAO-A, MAO-B, TH, VMAT2, DRD1, and DRD2.
The study revealed a significant reduction in dopamine levels in rats treated with paroxetine, both 24 hours after the final dose and one-month post-treatment, compared to controls. Additionally, gene expression analysis showed increased MAO-A during treatment and altered expressions of TH, VMAT2, DRD1, and DRD2 during the suspension period. These findings indicate that paroxetine alters dopamine pathways in NAc, suggesting modification linked to sexual motivation, and may contribute to PSSD. Ongoing experiments may deepen these results.
Paroxetine significantly affects dopamine signaling in NAc, both during and after treatment. This study offers new insights into the mechanisms behind PSSD, suggesting that SSRIs may cause long-term alterations in brain function, particularly in regions related to motivation and sexual behavior.
Authors declare no conflict of interest.