title: Effects of dexmedetomidine, midazolam, and propofol on acetylcholine release in the rat cerebral cortex in vivo.
abstract: Acetylcholine plays an important role as a neurotransmitter in the central nervous system with involvement in both sleep and arousal. Dexmedetomidine, midazolam, and propofol are widely used for sedation of patients in intensive care medicine. In this study, we have examined the effect of continuous administration of dexmedetomidine, midazolam, and propofol on acetylcholine release in the rat cerebral cortex, using an in vivo microdialysis technique. Following infusion of a control solution, male Wistar rats (n = 6/group) were administered dexmedetomidine at 0.3 μg/kg/min, midazolam at 20 mg/kg/h, or propofol at 50 mg/kg/h over a 2-h period. Using a brain microdialysis method, extracellular acetylcholine concentrations were measured up to 2 h after administration of each agent at 15-min intervals. In the midazolam group, acetylcholine levels were significantly reduced with midazolam infusion, remaining low even after the drug was stopped. In the propofol group, acetylcholine levels were significantly decreased during propofol infusion, but returned to control levels once the infusion was stopped. Dexmedetomidine administration decreased acetylcholine release, but this finding was not statistically significant. From this study, midazolam and propofol but not dexmedetomidine significantly suppressed acetylcholine release in the cerebral cortex at sedative doses. Even though the righting reflex recovered almost the same after the cessation of drug administration, midazolam suppressed acetylcholine release longer than propofol.
authors.affiliation: Department of Anesthesiology, Fukushima Medical University School of Medicine, Hikarigaoka-1, Fukushima, Fukushima, 960-1295, Japan, nemo@fmu.ac.jp.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nemoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Murakawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hakozaki
authors.forename: Tuyoshi
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Tuyoshi
authors.initials: T
authors.lastname: Isosu
authors.forename: Shinju
authors.initials: S
authors.lastname: Obara
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D020927:Dexmedetomidine / Q000494:pharmacology*; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020927:Dexmedetomidine; D000109:Acetylcholine; D008874:Midazolam; D015742:Propofol