Excessive release of [H-3]noradrenaline and glutamate in response to simulation of ischemic conditions in rat spinal cord slice preparation: effect of NMDA and AMPA receptor antagonists

In the present study we investigated the effects of NMDA and non-NMDA gluta mate receptor antagonists on the ischemia-evoked release of [H-3]noradrenal ine from rat spinal cord slices. An in vitro ischemia model (oxygen and glu cose deprivation) was used to simulate the ischemic conditions known to cau se neuronal injury. Spinal cord slices were loaded with [H-3]noradrenaline and superfused with Krebs solution in a micro-organ bath. Both axonal stimu lation and ischemia increased the release of [H-3]noradrenaline, but the re lease in response to glucose and oxygen deprivation was [Ca2+](o) independe nt. Dizocilpine (MK-801), an NMDA receptor antagonist, suppressed the relea se of [H-3]noradrenaline produced by ischemia, while it enhanced the releas e of [H-3]noradrenaline evoked by electrical field stimulation In contrast, LY300168 (GYKI-53655) [(+/-)-3-N-methylcarbamyde-1-(4-aminophenyl)-3-methy l-1.8-methylene-dioxy-5H-2.3-benzodiazepine] and its (-)isomer LY303070 (GY KI-53784) [(-)-3-N-methylcarbamyde-1-(4-aminophenyl)-4-methyl-1.8-methylene -dioxy-5H-2.3-benzodiazepine] AMPA receptor antagonists, had no effect on t he release of [H-3]noradrenaline evoked by either electrical stimulation or ischemia. Desipramine, a noradrenaline uptake inhibitor, potentiated the r elease of [H-3]noradrenaline evoked by ischemia, while in the absence of [C a2+](o) but under conditions when [H-3]noradrenaline release was further in creased, it reduced the release. Dizocilpine also decreased glutamate and a spartate release, measured by high performance liquid chromatography, durin g ischemia. It is concluded that glutamate release and NMDA receptors, but not AMPA receptors, are involved in the acute effect of oxygen and glucose deprivation on the excessive release of noradrenaline and that this release is not related to physiological axonal conduction. (C) 1999 Elsevier Scien ce B.V. All rights reserved.