Inhibition of glutamate transporters increases the minimum alveolar concentration for isoflurane in rats

Background. Glutamate transporters [also named excitatory aminoacid transporters (EAATs)] bind and take up extracellular glutamate,a major excitatory neurotransmitter, and can regulate glutamatergicneurotransmission in synapses. As anaesthesia is proposed tobe induced by enhancing inhibitory neurotransmission, inhibitingexcitatory neurotransmission, or both we hypothesize that inhibitionof EAAT activity can increase the anaesthetic requirement. Methods. The minimum alveolar concentration (MAC, the anaestheticconcentration required to suppress movement in response to noxiousstimulation in 50% of subjects) for isoflurane was determinedin adult male Sprague–Dawley rats after intrathecal administrationof EAAT inhibitors. Results. Application of DL-threo-ß-benzyloxyaspartate,a selective EAAT inhibitor, dose- and time-dependently increasedthe MAC for isoflurane. The MAC was 109 (1)% and 116 (4)% ofthe baseline, respectively, for 0.2 and 0.4 µmol of DL-threo-ß-benzyloxyaspartate15 min after the injection of the drug (n=5, P<0.05 comparedwith the baseline MAC). Intrathecal injection of dihydrokainate,a selective inhibitor of EAAT type 2, also increased the MACfor isoflurane. Conclusions. These results suggest that EAAT in the spinal cordcan regulate the requirement of isoflurane to induce immobility.EAAT2 may be involved in this effect.