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Passively administered fluoxetine reaches the juvenile brain of FSL rats and reduces antioxidant defences, without altering serotonin turnover.
- Source :
-
BMC pharmacology & toxicology [BMC Pharmacol Toxicol] 2024 Aug 16; Vol. 25 (1), pp. 51. Date of Electronic Publication: 2024 Aug 16. - Publication Year :
- 2024
-
Abstract
- Background: Fluoxetine is present in breast milk, yet it is unclear to what extent it, or its active metabolite, norfluoxetine, reaches the brain of the infant and what the effects of such exposure on neurobiological processes are. We therefore aimed to quantify the concentration of passively administered fluoxetine and norfluoxetine in the whole brains of exposed Flinders sensitive line (FSL) offspring and establish their influence on serotonergic function and redox status.<br />Methods: Adult FSL dams received fluoxetine (10 mg/kg/day), or placebo for fourteen days, beginning on postpartum day 04. Offspring were passively exposed to fluoxetine until postnatal day 18 and euthanized on postnatal day 22. Whole brain fluoxetine, norfluoxetine, serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and reduced (GSH) and oxidized glutathione (GSSG) concentrations were measured via liquid chromatography-mass spectrometry (LC-MS) analysis.<br />Results: Whole-brain serotonin and 5-hydroxyindoleacetic acid concentrations, and serotonin turnover (5-HIAA/5-HT) were comparable between strains. Treatment-naïve FSL rats had lower GSH and higher GSSG whole-brain concentrations, relative to FRL controls, and an overall decreased GSH/GSSG ratio. Passively administered fluoxetine resulted in undetectable whole-brain concentrations, while norfluoxetine averaged 41.28 ± 6.47 ng/g. Serotonin turnover of FSL rats was unaffected by passively administered fluoxetine, while redox status (GSH/GSSG) was decreased.<br />Conclusion: Our findings confirm that passively administered fluoxetine reaches the infant brain in the form of norfluoxetine and may manipulate processes of oxidative stress regulation. Further studies into the long-term bio-behavioural effects are however needed to effectively inform breast feeding mothers on the safety of antidepressant-use.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Female
Rats
Antioxidants metabolism
Antioxidants pharmacology
Male
Pregnancy
Glutathione metabolism
Fluoxetine analogs & derivatives
Fluoxetine pharmacology
Serotonin metabolism
Brain metabolism
Brain drug effects
Selective Serotonin Reuptake Inhibitors administration & dosage
Selective Serotonin Reuptake Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2050-6511
- Volume :
- 25
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC pharmacology & toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 39152503
- Full Text :
- https://doi.org/10.1186/s40360-024-00775-1