抄録
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 γ-aminobutyric acid (GABA) at the GABA type A receptors, but the influence of Fluox on the brain and serum levels of a neuroactive androgen, 5α-androstane-3α,17β-diol (3α,5α-Adiol), is poorly understood. In this study, we examined the Fluox-evoked changes in the 3α,5α-Adiol levels and compared the level changes of 3α,5α-Adiol with those of AP. The brain and serum 3α,5α-Adiol and AP levels were determined using previously developed LC-MS/MS. The ratio of the brain 3α,5α-Adiol to the serum 3α,5α-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 3α,5α-Adiol was much lower than that in AP, this study demonstrated that the 3α,5α-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 3α-hydroxysteroid dehydrogenase enzyme followed by the promotion of the de novo biosynthesis of 3α,5α-Adiol in the brain.
