This study was designed to evaluate the ability of dexmedetomidine, an α2-adrenergic agonist, to attenuate increases in the hippocampal concentration of extracellular glutamate and glycine that result from episodes of transient global cerebral ischemia. After the induction of anesthesia with halothane and oxygen, microdialysis catheters were stereotactically inserted into the hippocampi of 16 New Zealand white rabbits. After the collection of baseline samples of dialysate, animals were randomly assigned to receive an intravenous infusion of either saline (n= 8) or dexmedetomidine (n= 8). Transient global cerebral ischemia was produced by the inflation of a neck tourniquet and induction of deliberate hypotension for 10 min. Dialysates were collected during the ischemic period and for the ensuing 60 min of reperfusion. During ischemia, the concentrations of glutamate and glycine increased from the preischemic baseline in both groups. Glutamate concentrations rapidly returned to baseline after reperfusion, whereas glycine concentrations remained elevated throughout the reperfusion period. There were no significant differences between the control and dexmedetomidine-treated groups. These results suggest that the mechanism of the putative neuroprotective effects of dexmedetomidine is not related to decreased concentrations of glutamate or glycine.