Chronic neurosteroid treatment attenuates single cell GABAA response and its potentiation by modulators in cortical neurons

• Published in: Brain research 1996-01, Vol.706 (1), p.160-162
• Main Authors: YU, R, HAY, M, TICKU, M. K
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Down-Regulation; Fundamental and applied biological sciences. Psychology; GABA Modulators - pharmacology; Mice; Mice, Inbred C57BL; Neurons - drug effects; Pentobarbital - pharmacology; Pregnanolone - pharmacology; Radioligand Assay; Receptors, GABA-A - drug effects; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)01247-8

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.