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Modulation by neurosteroids of the in vivo (+)‐[ 3 H]SKF‐10,047 binding to σ 1 receptors in the mouse forebrain
Author(s) -
Maurice Tangui,
Roman François J.,
Privat Alain
Publication year - 1996
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19961215)46:6<734::aid-jnr10>3.0.co;2-u
Subject(s) - pregnenolone sulfate , neuroactive steroid , pregnenolone , sigma receptor , in vivo , endocrinology , medicine , forebrain , receptor , hippocampus , chemistry , dehydroepiandrosterone sulfate , dehydroepiandrosterone , pharmacology , biology , central nervous system , steroid , hormone , gabaa receptor , microbiology and biotechnology , androgen
Recent reports suggest an interaction between neuro‐(active)steroids and sigma 1 (σ 1 ) receptors, affecting biochemical parameters as well as physiological responses mediated by σ 1 ligands in the rodent brain. In this study, we examined the modulation by neurosteroids of the haloperidol‐sensitive in vivo (+)‐[ 3 H]SKF‐10,047 binding to σ 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 (+)‐[ 3 H]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 (+)‐[ 3 H]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 σ 1 receptors, and show that physiologic modulations of the steroidal concentrations affect the σ 1 systems. © 1996 Wiley‐Liss, Inc.