INVESTIGATIONS OF NEUROTOXICITY AND NEUROPROTECTION WITHIN THE NUCLEUS BASALIS OF THE RAT

The present study investigated the specific ways by which cytotoxicity due to glutamate receptor stimulation could be attenuated by the admi nistration of agonists and antagonists of the ionotropic and metabotro pic glutamate receptors within the nucleus basalis magnocellularis (NB M) of rats as measured by cortical choline acetyltransferase activity. The results of these studies suggest that (1) the cytotoxicity of ibo tenate to NBM cholinergic cells is not dependent upon stimulation of m etabotropic glutamate receptors, but results from activation of N-meth yl-D-aspartate (NMDA) receptors, (2) the cytotoxicity of quisqualate t o cholinergic cells within the NBM is not dependent upon stimulation o f NMDA or metabotropic receptors, and (3) the cytotoxicity of NMDA was prevented by administration (i.p.) of the un-competitive NMDA antagon ist memantine (30 mg/kg), resulting in plasma levels of 2.5 mu g/ml, a concentration known to block efficiently NMDA receptors in vitro. Fin ally, performance of a food-motivated, delayed-alternation task on a T -maze was impaired by injections of NMDA into the NBM, but was prevent ed by co-administration of NMDA with memantine.