Differential Effects of NMDA and AMPA/Kainate Receptor Antagonists on Superoxide Production and MnSOD Activity in Rat Forebrain Cortex Following Intrahippocampal Injection

Radenovic L, Selakovic V, Kartelija G

Department of Physiology and Biochemistry, Faculty of Biology, University of Belgrade,

The involvement of ionotropic glutamate NMDA and AMPA/kainate receptors in the induction of superoxide radical production in the rat forebrain cortex was examined after intrahippocampal injection of kainate, non-NMDA receptor agonist, kainate plus 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), selective AMPA/kainate receptor antagonist, or kainate plus 2-amino-5-phosphonopentanoic acid (APV), selective NMDA receptor antagonist. Competitive glutamate receptor antagonists (0.5 mg/ml) were injected with kainate unilaterally into the CA3 region of the rat hippocampus. We investigated superoxide production and mitochondrial MnSOD activity after injection. The measurements took place at different times (5 min, 15 min, 2 h, 48 h and 7 days) in the ipsi- and contralateral forebrain cortex. Stimulation of glutamate receptors induces superoxide production and modulates activity of mitochondrial MnSOD, an inducible enzyme with the potential to protect neurons by its superoxide activity. Used glutamate antagonists APV and CNQX both expressed sufficient neuroprotection in sense of decreasing superoxide production and increasing MnSOD levels, but with differential effect in mechanisms and time dynamics. Our findings suggest that NMDA and AMPA/kainate receptors are differentially involved in superoxide production. Following intrahippocampal antagonists injection they, also, interpose different neuroprotection effect on the induction of MnSOD activity in forebrain cortex.

Email: lira@ibiss.bg.ac.yu

Address: Department of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski trg 16, p.f. 52, 11000 Belgrade, Serbia and Montenegro