{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:42:11Z","timestamp":1791160931625,"version":"4.1.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,11]]},"abstract":"Abstract<\/jats:title>\n \n Background:<\/jats:title>\n \n It has been shown that \u03b3-aminobutyric acid exerts excitatory actions on the immature brain due to the increased expression of Na\n +<\/jats:sup>\n \u2013K\n +<\/jats:sup>\n \u20132Cl\n \u2212<\/jats:sup>\n cotransporter isoform 1. The authors sought to clarify whether midazolam, a \u03b3-aminobutyric acid\u2013mimetic hypnotic agent, causes neuronal excitation that can be blocked by bumetanide, a selective inhibitor of Na\n +<\/jats:sup>\n \u2013K\n +<\/jats:sup>\n \u20132Cl\n \u2212<\/jats:sup>\n cotransporter isoform 1. Furthermore, the authors examined whether bumetanide potentiates the sedative effects of midazolam in neonatal rats.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n The authors measured the effects of midazolam with or without bumetanide on the cytosolic Ca\n 2+<\/jats:sup>\n concentration ([Ca]\n 2+<\/jats:sup>\n i<\/jats:sub>\n ) in hippocampal slices (n = 3 in each condition) from rats at postnatal days 4, 7, and 28 (P4, P7, and P28) using fura-2 microfluorometry. Neuronal activity in the hippocampus and thalamus after intraperitoneal administration of midazolam with or without bumetanide was estimated by immunostaining of phosphorylated cyclic adenosine monophosphate\u2013response element\u2013binding protein (n = 12 in each condition). Furthermore, the authors assessed effects of bumetanide on the sedative effect of midazolam by measuring righting reflex latency (n = 6 in each condition).\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Midazolam significantly increased [Ca]\n 2+<\/jats:sup>\n i<\/jats:sub>\n in the CA3 area at P4 and P7 but not at P28. Bumetanide inhibited midazolam-induced increase in [Ca]\n 2+<\/jats:sup>\n i<\/jats:sub>\n . Midazolam significantly up-regulated phosphorylated cyclic adenosine monophosphate\u2013response element\u2013binding protein expression in a bumetanide-sensitive manner in the hippocampus at P7 but not P28. Bumetanide enhanced the sedative effects of midazolam in P4 and P7 but not P28 rats.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n These results suggest that \u03b3-aminobutyric acid A receptor\u2013mediated excitation plays an important role in attenuated sedative effects of midazolam in immature rats.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/aln.0b013e31829e4b05","type":"journal-article","created":{"date-parts":[[2013,6,19]],"date-time":"2013-06-19T08:20:45Z","timestamp":1371630045000},"page":"1096-1108","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Bumetanide, an Inhibitor of Cation-chloride Cotransporter Isoform 1, Inhibits \u03b3-Aminobutyric Acidergic Excitatory Actions and Enhances Sedative Actions of Midazolam in Neonatal Rats"],"prefix":"10.1097","volume":"119","author":[{"given":"Yukihide","family":"Koyama","sequence":"first","affiliation":[{"name":"Graduate Course 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