title: Excitatory and inhibitory actions of isoflurane on the cholinergic ascending arousal system of the rat.
abstract: BACKGROUND
  The cholinergic arousal systems are known to critically regulate the state of consciousness. The aim of this study was to determine the effect of isoflurane on the inhibitory or excitatory neurotransmitters efflux in important nuclei within the cholinergic arousal system using in vivo intracerebral microdialysis.
  
  
  METHODS
  The efflux of glutamate, gamma-aminobutyric acid (GABA), or acetylcholine in the posterior hypothalamus (PH), the basal forebrain (BF), and the somatosensory cortex (S1BF) of rats was detected using intracerebral microdialysis under an awake condition and at 0.5-2.0 minimum alveolar concentration (MAC) isoflurane anesthesia. The intrabasalis perfusion of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate on the cortical acetylcholine effluxes was also examined under both conditions.
  
  
  RESULTS
  Isoflurane had no influence on the glutamate and GABA efflux in the PH, whereas in the BF, it dose-dependently increased glutamate efflux and decreased GABA efflux. A transient increase in glutamate efflux at 1.0 MAC and a decrease in GABA at 0.5-1.5 MAC were observed in the S1BF. Isoflurane dose-dependently decreased acetylcholine efflux in the S1BF. Perfusion of the BF with AMPA increased acetylcholine efflux in the S1BF with electroencephalographic activation during 0.75 MAC isoflurane anesthesia, suggesting an inhibitory action of isoflurane on AMPA receptors in the BF. However, N-methyl-D-aspartate had no effect on these parameters.
  
  
  CONCLUSIONS
  Isoflurane induces both excitatory and inhibitory actions in the cholinergic arousal system. The predominant inhibitory action of isoflurane over its excitatory action at the BF would result in the decrease in the acetylcholine efflux in the S1BF.
authors.affiliation: Department of Anesthesiology & Reanimatology, Faculty of Medical Science, University of Fukui, Fukui, Japan.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Dong
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukuda
authors.forename: Eri
authors.initials: E
authors.lastname: Murata
authors.forename: Takashi
authors.initials: T
authors.lastname: Higuchi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D018685:Anesthetics, Inhalation; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D007530:Isoflurane; D008297:Male; D017551:Microdialysis; D010275:Parasympathetic Nervous System; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D007530:Isoflurane; D000109:Acetylcholine