Studies on Neurosteroids XXVI. Fluoxetine-Evoked Changes in Rat Brain and Serum Levels of Neuroactive Androgen, 5.ALPHA.-Androstane-3.ALPHA.,17.BETA.-diol
| Autor: | Kazutake Shimada, Toshimasa Toyo'oka, Yukiko Nagura, Tatsuya Higashi |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Neuroactive steroid medicine.drug_class Serotonin reuptake inhibitor Pharmaceutical Science Pharmacology chemistry.chemical_compound Fluoxetine Internal medicine medicine Animals Rats Wistar Receptor chemistry.chemical_classification Neurotransmitter Agents Chemistry Allopregnanolone Brain General Medicine Androgen Androstane-3 17-diol Rats Endocrinology Enzyme Androgens Androstane medicine.drug |
| Zdroj: | Biological and Pharmaceutical Bulletin. 32:1636-1638 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.32.1636 |
| Popis: | It is well known that fluoxetine (Fluox), a selective serotonin reuptake inhibitor, increases the brain content of allopregnanolone (AP), a potent neuroactive steroid that positively modulates the action of gamma-aminobutyric acid (GABA) at the GABA type A receptors, but the influence of Fluox on the brain and serum levels of a neuroactive androgen, 5alpha-androstane-3alpha,17beta-diol (3alpha,5alpha-Adiol), is poorly understood. In this study, we examined the Fluox-evoked changes in the 3alpha,5alpha-Adiol levels and compared the level changes of 3alpha,5alpha-Adiol with those of AP. The brain and serum 3alpha,5alpha-Adiol and AP levels were determined using previously developed LC-MS/MS. The ratio of the brain 3alpha,5alpha-Adiol to the serum 3alpha,5alpha-Adiol concentrations (B/S value) was significantly elevated in the rats intraperitoneally administered Fluox (10 mg/kg). Although the magnitude of the Fluox-evoked level change in 3alpha,5alpha-Adiol was much lower than that in AP, this study demonstrated that the 3alpha,5alpha-Adiol content is also influenced by Fluox. The most probable cause for the increase in the B/S value by the Fluox treatment is the activation of the 3alpha-hydroxysteroid dehydrogenase enzyme followed by the promotion of the de novo biosynthesis of 3alpha,5alpha-Adiol in the brain. |
| Databáze: | OpenAIRE |
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