A Comparison of the Effect of Halothane on N-Methyl-D-Aspartate and Non-N-Methyl-D-Aspartate Receptor-Mediated Excitatory Synaptic Transmission in the Hippocampus

Abstract

Halothane depresses synaptic transmission in the rat brain. First we determined the concentration of halothane which decreased the amplitude of the population spike recorded in the CA1 region of the hippocampus to 50% of the control value (105 +/- 4.9 micrograms/mL [0.53 mM] halothane). Hippocampal glutamate receptors are divided into N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA) and kainate (non-NMDA) subtypes. The NMDA and non-NMDA receptors were blocked with (+/-)-2-amino-5-phosphonopentanoic acid (AP5) (30 microM), and 6,7-dinitroquinoxaline-2,3-dione (DNQX) (10 microM), respectively, to allow observation of the effects of halothane on the NMDA and non-NMDA receptors, respectively. gamma-Aminobutyric acid type A (GABAA) receptors were blocked in all studies with picrotoxin (PTX) (40 microM). When the non-NMDA receptors were blocked a halothane concentration of 38.1 +/- 5.6 mg/mL was required to produce a further 50% decrease in population spike amplitude. When NMDA receptors were blocked with AP5 or only GABAA receptors were blocked the halothane concentrations needed to produce 50% block were higher than needed for the control (160.8 +/- 17.8 and 190.2 +/- 12.1 microgram/mL, respectively). These studies indicate that the NMDA receptors are more sensitive to the effects of halothane than the non-NMDA receptors.