title: Modulation by neurosteroids of the in vivo (+)-[3H]SKF-10,047 binding to sigma 1 receptors in the mouse forebrain.
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.
authors.affiliation: INSERM U. 336, Ecole Nationale Supérieure de Chimie, Montpellier, France.
authors.forename: T
authors.initials: T
authors.lastname: Maurice
authors.forename: F J
authors.initials: FJ
authors.lastname: Roman
authors.forename: A
authors.initials: A
authors.lastname: Privat
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001667:Binding, Competitive / Q000502:physiology; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011247:Pregnancy; D011284:Pregnenolone / Q000378:metabolism / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D016548:Prosencephalon / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000378:metabolism*; D014316:Tritium
chemical_list: D014150:Antipsychotic Agents; D012739:Gonadal Steroid Hormones; D017480:Receptors, sigma; C018370:pregnenolone sulfate; D014316:Tritium; D011374:Progesterone; D019314:Dehydroepiandrosterone Sulfate; D011284:Pregnenolone; C012134:SK&F 10047; D010620:Phenazocine