Effects of isoflurane on in vivo release of acetylcholine in the rat cerebral cortex and striatum

Background : Acetylcholine (ACh) is one of the major excitatory neurotransmitters in the central nervous system, and changes in neural activity induced by anesthesia alter the release of ACh. However, the effects of isoflurane, one of the most widely used volatile anesthetics, on ACh release are not known. The present study attempts to clarify the dose–effect relationship of isoflurane on the in vivo release of ACh in rat brains.
Methods : Changes in the extracellular concentration of ACh and choline in the cerebral cortex and striatum induced by 0.5, 1.0, and 1.5 minimum alveolar concentration (MAC) of isoflurane were determined using a brain microdialysis technique.
Results : In the cortex, the ACh release decreased to 30.8±10.1 (mean±SEM), 10.2±4.1, and 8.1±2.9% of basal value by increasing doses of isoflurane, and in the striatum, to 73.3±4.4, 49.2±4.2, and 40.7±4.5%. The ACh release rapidly recovered control levels with the discontinuance of isoflurane. Choline concentration was not changed significantly by isoflurane except for a decrease to 74.8±4.6% in the striatum by 0.5 MAC. In both the cortex and striatum, the choline concentration decreased with the discontinuance of isoflurane to 70.3±13.3, and 68.2±5.4%, respectively.
Conclusion : The fact that all classic anesthetics reported previously, as well as isoflurane, reduce ACh release supports the hypothesis that the suppression of cholinergic cells is, at least in part, one of the mechanisms of anesthesia.