MODULATION OF ISCHEMIC EXCITATORY NEUROTRANSMITTER AND GAMMA-AMINOBUTYRIC-ACID RELEASE DURING GLOBAL TEMPORARY CEREBRAL-ISCHEMIA BY SELECTIVE NEURONAL NITRIC-OXIDE SYNTHASE INHIBITION

Nitric oxide release during cerebral ischemia is the result of both ne uronal and endothelial subclasses of nitric oxide synthase (NOS). In t his study, we examined the role of specific neuronal NOS inhibition (n NOSI) on excitatory neurotransmitter and gamma-aminobutyric acid (GABA ) release during global cerebral ischemia. Microdialysis probes were p laced into the striatum of 24 rats. After probe stabilization, rats we re randomized to receive 7-nitroindazole (7-NI), a selective nNOSI, in doses of 0, 5, 10, or 20 mg/kg. Temporary global forebrain ischemia w as induced for 15 min, followed by 60 min of reperfusion, nNOSI admini stration did not produce detectable changes in neurotransmitter recove ry prior to ischemia. There were significant increases in aspartate (A SP), glutamate (GLU), glycine (GLY), and GABA recovery during ischemia in the absence of nNOSI. 7-NI resulted in an attenuation in GLU, GLY, and GABA recovery during ischemia and reperfusion. No differences in ASP recovery were detected with nNOSI. Differences between the present study and other studies that examine the role of nonspecific constitu tive NOSI during cerebral ischemia demonstrate the contribution of neu ronal NOS on the modulation of ischemic excitatory neurotransmitter an d GABA release.