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• W2023942005 abstract "Allosteric modulation by neuroactive steroids of radioligand binding sites on the GABAA receptor complex was demonstrated by autoradiography in vitro in several regions of human brain and the effects compared to those in rat brain. Comparing human and rat, two steroids known to be active in enhancing GABA-mediated postsynaptic inhibition, 5 alpha-pregnane-3 alpha,21-diol-20-one (tetrahydro-deoxycorticosterone, THDOC) and alphaxalone (5 alpha-pregnane-3 alpha-hydroxy-11,20-dione), allosterically inhibited [35S]T-BPS binding to the picrotoxin/convulsant site in both species in several regions including the hippocampus. Unlike rat, human brain binding of [3H]flunitrazepam to the benzodiazepine site was not enhanced by alphaxalone (at any concentration), but was unaffected in many regions and inhibited in others. Binding of [3H]muscimol to high and low affinity GABA sites were enhanced by both steroids in all tested regions of rat brain, although to varying degrees. However, several lobes of human cortex showed no modulation of muscimol binding by either steroid, and THDOC, but not alphaxalone, inhibited in some areas. Comparing regions, THDOC at high concentrations (10 microM) enhanced in human frontal lobe and primary sensory and motor cortex, with greater effect in deep layers than superficial. This steroid had no effect in other parts of parietal lobe and inhibited muscimol binding in temporal lobe, primary visual cortex, and other parts of occipital lobe. Concentration-dependence curves for THDOC showed regional variation, e.g., in the hippocampal formation and surrounding neocortex. These regional and species differences are consistent with the existence of multiple GABAA receptor subtypes that differ in pharmacology. This heterogeneity provides both the opportunity and the difficulty of targeting clinically useful medications such as antiepileptic drugs to the appropriate human brain regions, and the species differences in regional subtype expression suggest caution in use of animal models." @default.
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• W2023942005 date "1995-02-01" @default.
• W2023942005 modified "2023-09-25" @default.
• W2023942005 title "Modulation of GABAA receptor binding in human brain by neuroactive steroids: Species and brain regional differences" @default.
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• W2023942005 doi "https://doi.org/10.1002/syn.890190203" @default.
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