caa a22 4500 469119705 CHVBK 20180323133135.0 cr unu---uuuuu 170328e19920701xx s 000 0 eng 10.1007/BF02245313 doi (NATIONALLICENCE)springer-10.1007/BF02245313 Dexmedetomidine synergism with midazolam in the elevated plus-maze test in rats [Elektronische Daten] [Markku Salonen, Emmanuel Onaivi, Mervyn Maze] The anxiolytic profile of dexmedetomidine, a novel, highly-selective α2-adrenergic agonist, was examined in rats in the elevated plus-maze test when administered either alone or in combination with the benzodiazepine agonist midazolam. Dexmedetomidine, 0.1-10 µg/kg, was inactive in modifying the rats' behavioral response in this test. Midazolam, 0.1-10 mg/kg, dose-dependently produced an anxiolytic-like profile characterized by an increased time spent in the open arms of the elevated plus-maze. A combination of dexmedetomidine 0.5 µg/kg and midazolam 0.5 mg/kg produced a synergistic interaction. This heterergic interaction of dexmedetomidine on midazolam's anxiolytic-like profile was dose-dependently blocked by pretreatment with an α2-adrenergic antagonist, atipamezole, 10-50 µg/kg, and a benzodiazepine antagonist flumazenil, 1.0 and 10 mg/kg, but not by the α1-adrenergic antagonist, prazosin, 0.1-10 mg/kg. While the transmembrane signal transduction pathways for benzodiazepine- and α2-agonist responses do not share any molecular component, there does appear to be "crosstalk” between these two systems. These may involve GABA or noradrenergic "downstream” effects of either dexmedetomidine or midazolam, respectively. Springer-Verlag, 1992 Anxiolysis nationallicence Benzodiazepine agonist, midazolam nationallicence Benzodiazepine antagonist, flumazenil nationallicence α2-Adrenergic agonists, dexmedetomidine nationallicence α-Adrenergic antagonists, atipamezole nationallicence α1-Adrenergic antagonists, prazosin nationallicence Elevated plus-maze nationallicence Rat nationallicence Salonen Markku Department of Anesthesia, Stanford University, 94304, Palo Alto, CA, USA aut Onaivi Emmanuel Department of Anesthesia, Stanford University and Molecular Research Institute, 94304, Palo Alto, CA, USA aut Maze Mervyn Department of Anesthesia, Stanford University, and Staff Physician, Veterans Affairs Hospital, 94304, Palo Alto, CA, USA aut Psychopharmacology Springer-Verlag 108/1-2(1992-07-01), 229-234 0033-3158 108:1-2<229 1992 108 213 https://doi.org/10.1007/BF02245313 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02245313 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Salonen Markku Department of Anesthesia, Stanford University, 94304, Palo Alto, CA, USA aut NATIONALLICENCE 700 1- Onaivi Emmanuel Department of Anesthesia, Stanford University and Molecular Research Institute, 94304, Palo Alto, CA, USA aut NATIONALLICENCE 700 1- Maze Mervyn Department of Anesthesia, Stanford University, and Staff Physician, Veterans Affairs Hospital, 94304, Palo Alto, CA, USA aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 108/1-2(1992-07-01), 229-234 0033-3158 108:1-2<229 1992 108 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer