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Brain neurosteroid changes after paroxetine administration in mice
Allon Nechmad1, Rachel Maayan, Baruch Spivak
1Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Petah Tikva, Israel.
Summary
Selective serotonin reuptake inhibitors (SSRIs) like paroxetine show a delayed mood-elevating effect. This study suggests brain allopregnanolone (THP) synthesis, influenced by SSRI treatment duration, may explain the antidepressant delay.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Selective serotonin reuptake inhibitors (SSRIs) have a known delay in antidepressant effects.
- Neurosteroids like allopregnanolone (THP) possess mood-elevating properties and are affected by SSRIs.
Purpose of the Study:
- To investigate the time-dependent effects of paroxetine on neurosteroid synthesis in the brain.
- To compare brain and peripheral synthesis of THP and its precursor, 5alpha-dihydroprogesterone (DHP).
Main Methods:
- Mice were administered paroxetine intraperitoneally for 9 and 21 days.
- Synthesis levels of DHP and THP were measured in the cortex, hypothalamus, and olfactory bulb.
- Peripheral DHP and THP levels were assessed in serum.
Main Results:
- Brain DHP synthesis increased after 9 days of paroxetine, while THP synthesis increased significantly only after 21 days.
- Peripheral DHP increased after 9 days but returned to normal by 21 days; serum THP showed no increase.
- Brain and peripheral neurosteroid synthesis exhibited differential responses to paroxetine, indicating independent brain synthesis.
Conclusions:
- Paroxetine's duration of administration differentially affects brain synthesis of DHP and THP.
- Increased brain THP synthesis over time may underlie the delayed antidepressant and anxiolytic effects of SSRIs.