THE RELATIONSHIP BETWEEN GLUTAMATE RELEASE AND CEREBRAL BLOOD-FLOW AFTER FOCAL CEREBRAL-ISCHEMIA IN THE CAT - EFFECT OF PRETREATMENT WITH ENADOLINE (A KAPPA-RECEPTOR AGONIST)

The effect of the kappa-opioid agonist enadoline (CI-977) upon the rel ationship between cerebral blood flow and glutamate release was simult aneously assessed (using microdialysis and hydrogen clearance techniqu es respectively) at the same anatomical locus in the cerebral cortex ( suprasylvian gyrus) after permanent middle cerebral artery (MCA) occlu sion in halothane-anaesthetised cats. During controlled graded ischaem ia, pretreatment with enadoline (0.3 mg/kg i.v. followed by continuous infusion at 0.15 mg/kg/h), initiated 30 min prior to MCA occlusion, s ignificantly attenuated the marked increases in extracellular glutamat e, aspartate and GABA observed in the focal ischaemic penumbra. The pr esent data are consistent with the hypothesis that the neuroprotective efficacy of enadoline in focal cerebral ischaemia is due to inhibitio n of glutamate release in the ischaemic penumbra.