Chronic neurosteroid treatment attenuates single cell GABAA response and its potentiation by modulators in cortical neurons.
In previous studies we have observed that chronic neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one (5 alpha 3 alpha) treatment produced downregulation of the GABAA receptors, heterologous uncoupling, and decreased heterologous efficacy at the GABAA receptor complex in cultured mammalian cortical neurons. In this study, using whole cell recording, we examined the consequence of chronic 5 alpha 3 alpha (1 microM; 5 days) treatment on GABA-induced currents in isolated cortical neurons. We observed that the GABA current was decreased by 78% after 5 days treatment of cortical cells with 1 microM 5 alpha 3 alpha. We also observed decreased pentobarbital, and 5 alpha 3 alpha potentiation of GABA currents after chronic 5 alpha 3 alpha treatment. These findings support the notion that GABA response, and its potentiation by pentobarbital, and neurosteroid, 5 alpha 3 alpha, are attenuated after chronic 5 alpha 3 alpha treatment.
Yu
R
R
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764, USA.
Hay
M
M
Ticku
M K
MK
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D015536:Down-Regulation; D018757:GABA Modulators / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D010424:Pentobarbital / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology*; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000187:drug effects*
D018757:GABA Modulators; D011963:Receptors, GABA-A; D011280:Pregnanolone; D010424:Pentobarbital