Paroxetine effects in adult male rat colon: Focus on gut steroidogenesis and microbiota. (September 2022)

• Record Type: Journal Article
• Authors: Diviccaro, Silvia; Giatti, Silvia; Cioffi, Lucia; Falvo, Eva; Piazza, Rocco; Caruso, Donatella; Melcangi, Roberto C.
• Is Part Of: Psychoneuroendocrinology. Volume 143(2022)
• Publication Date: 2022-09
• Subjects: 3α-HSOR 3α-hydroxysteroid oxidoreductase -- 3α-diol 5α-androstane-3α, 17β-diol -- 5α-R1 5α-reductase type 1 -- 5α-R2 5α-reductase type 2 -- 17β-E 17β-estradiol -- ALLO Allopregnanolone -- APCI Atmospheric pressure chemical ionization -- AR Androgen receptor -- P450scc Cytochrome P450 side chain cleavage -- DHEA Dehydroepiandrosterone -- DHP Dihydroprogesterone -- DHT Dihydrotestosterone -- ENS Enteric nervous system -- GABA gamma-Aminobutyric acid -- GI Gastrointestinal -- IBD Inflammatory bowel disease -- ISOALLO Isoallopregnanolone -- LC-MS/MS Liquid chromatography tandem mass spectrometry analysis -- LC Liquid chromatography -- PSSD Post-SSRI sexual dysfunction -- PXR pregnane X receptor -- PREG Pregnenolone -- PROG Progesterone -- PR Progesterone receptor -- SSRI Selective serotonin reuptake inhibitors -- StAR Steroidogenic acute regulatory protein -- T Testosterone -- CB1R type 1 cannabinoid receptor; SSRI -- Sex steroids -- Pregnenolone -- Actinobacteria -- Cyanobacteria -- Firmicutes; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2022.105828
• Languages: English
• ISSNs: 0306-4530

Abstract

Abstract: Paroxetine, a selective serotonin reuptake inhibitor (SSRI), is prescribed to treat psychiatric disorders, although an off-label SSRI use is also for functional gastrointestinal disorders. The mutual correlation between serotonin and peripheral sex steroids has been reported, however little attention to sex steroids synthesized by gut, has been given so far. Indeed, whether SSRIs, may also influence the gut steroid production, immediately after treatment and/or after suspension, is still unclear. The finding that gut possesses steroidogenic capability is of particular relevance, also for the existence of the gut-microbiota-brain axis, where gut microbiota represents a key orchestrator. On this basis, adult male rats were treated daily for two weeks with paroxetine or vehicle and, 24 h after treatment and at 1 month of withdrawal, steroid environment and gut microbiota were evaluated. Results obtained reveal that paroxetine significantly affects steroid levels, only in the colon but not in plasma. In particular, steroid modifications observed immediately after treatment are not overlap with those detected at withdrawal. Additionally, paroxetine treatment and its withdrawal impact gut microbiota populations differently. Altogether, these results suggest a biphasic effect of the drug treatment in the gut both on steroidogenesis and microbiota. Highlights: Gut steroidogenesis is influenced by paroxetine treatment. Gut microbiota is influenced by paroxetine treatment. An increase of pregnenolone levels occurs at paroxetine withdrawal. Paroxetine withdrawal affects gut microbiota.