Modulation by neurosteroids of the in vivo (+)-[3H]SKF-10,047 binding to σ1 receptors in the mouse forebrain
✍ Scribed by Tangui Maurice; François J. Roman; Alain Privat
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 954 KB
- Volume
- 46
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Recent reports suggest an interaction between neuro-(active)steroids and sigma, (a,) receptors, affecting biochemical parameters as well as physiological responses mediated by u1 ligands in the rodent brain. In this study, we examined the modulation by neurosteroids of the haloperidol-sensitive in vivo (+)- [3H]SKF'-10,047 binding to u, sites in the mouse hippocampus and cortex. Progesterone (PROG; 2 4 0 mglkg), pregnenolone sulfate (PREGS; 10-40 mg/ kg), and dehydroepiandrosterone sulfate (DHEAS; 1 0 4 0 mg/kg) were administered systemically 10 min before the radioactive tracer. The total amount of ( +)-[3H]SKF-10,047 bound in each structure was significantly affected by PROG and PREGS only at the highest dose tested and was unaffected by DHEAS. However, bound to free (BIF) radioactivity ratios were highly significantly decreased by 3040% in each structure by PROG and PREGS. DHEAS, at 40 mglkg, induced a significant 20% decrease in the hippocampus. Furthermore, the in vivo ( + )-[3H]SKF-10,047 binding parameters were diminished in pregnant female mice compared to non-pregnant or male mice. These results confirm the in vitro binding results, bring a direct in vivo demonstration of the interaction between neurosteroids and u, receptors, and show that physiologic modulations of the steroidal concentrations affect the u1 systems.