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

Glutamate transporters [also named excitatory amino acid transporters (EAATs)] bind and take up extracellular glutamate, a major excitatory neurotransmitter, and can regulate glutamatergic neurotransmission in synapses. As anaesthesia is proposed to be induced by enhancing inhibitory neurotransmission, inhibiting excitatory neurotransmission, or both we hypothesize that inhibition of EAAT activity can increase the anaesthetic requirement.

The minimum alveolar concentration (MAC, the anaesthetic concentration required to suppress movement in response to noxious stimulation in 50% of subjects) for isoflurane was determined in adult male Sprague-Dawley rats after intrathecal administration of EAAT inhibitors.

Application of DL-threo-beta-benzyloxyaspartate, a selective EAAT inhibitor, dose- and time-dependently increased the MAC for isoflurane. The MAC was 109 (1)% and 116 (4)% of the baseline, respectively, for 0.2 and 0.4 micromol of DL-threo-beta-benzyloxyaspartate 15 min after the injection of the drug (n=5, P<0.05 compared with the baseline MAC). Intrathecal injection of dihydrokainate, a selective inhibitor of EAAT type 2, also increased the MAC for isoflurane.

These results suggest that EAAT in the spinal cord can regulate the requirement of isoflurane to induce immobility. EAAT2 may be involved in this effect.