Transcriptomic Profile of the Male Rat Hypothalamus and Nucleus Accumbens After Paroxetine Treatment and Withdrawal: Possible Causes of Sexual Dysfunction
Giatti, Silvia; Cioffi, Lucia; Diviccaro, Silvia; Chrostek, G.; Piazza, R.; Melcangi, Roberto Cosimo
Molecular Neurobiology2024
Summary (paraphrased)
RNA-seq of hypothalamus and nucleus accumbens in male rats treated with paroxetine for 2 weeks and re-examined after 1 month of withdrawal. The nucleus accumbens showed 245 differentially expressed genes at end of treatment and 6 persisting at withdrawal, including dopamine-, glutamate-, GABA-, neurexin/neuroligin-, and BDNF-signaling genes, alongside an inflammatory/immune-activation signature. The authors interpret the persisting changes as a molecular substrate for PSSD.
Plain-language summary (paraphrased)
After giving rats paroxetine and then stopping it, researchers found lasting changes in which genes were switched on in the brain's motivation and pleasure center. Most changes reversed, but a handful persisted — a concrete molecular demonstration of how an SSRI can leave a lasting imprint on the circuits that drive sexual desire.
Why it’s in the corpus
Directly PSSD-focused: full transcriptome of paroxetine treatment and withdrawal in sexual-behavior brain circuits, one of the few animal models of PSSD etiopathogenesis. NOTE: discord label 'CYP2D and SSRI response' is incorrect; PMID 39495228 is this Giatti paroxetine transcriptomics paper.
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