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  • Title: Modulation by neurosteroids of the in vivo (+)-[3H]SKF-10,047 binding to sigma 1 receptors in the mouse forebrain.
    Author: Maurice T, Roman FJ, Privat A.
    Journal: J Neurosci Res; 1996 Dec 15; 46(6):734-43. PubMed ID: 8978508.
    Abstract:
    Recent reports suggest an interaction between neuro-(active)steroids and sigma1 (sigma 1) receptors, affecting biochemical parameters as well as physiological responses mediated by sigma 1 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 sigma 1 sites in the mouse hippocampus and cortex. Progesterone (PROG; 2-40 mg/kg), pregnenolone sulfate (PREGS; 10-40 mg/kg), and dehydroepiandrosterone sulfate (DHEAS; 10-40 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 (B/F) radioactivity ratios were highly significantly decreased by 30-40% in each structure by PROG and PREGS. DHEAS, at 40 mg/kg, 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 sigma 1 receptors, and show that physiologic modulations of the steroidal concentrations affect the sigma 1 systems.
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