NEUROPROTECTION AGAINST N-METHYL-D-ASPARTATE-INDUCED EXCITOTOXICITY IN RAT MAGNOCELLULAR NUCLEUS BASALIS BY THE 5-HT1A RECEPTOR AGONIST 8-OH-DPAT

The present study reports the neuroprotective efficacy of the 5-HT1A r eceptor agonists 8-hydroxy- 2-(di-n-propylamino)tetralin (8-OH-DPAT) a nd ipsapirone against in vivo excitotoxic neuronal injury. Excitotoxic cell death was induced by injections of N-methyl-D-aspartate (NMDA) i n the rat magnocellular nucleus basalis. The neurodegenerative effects were quantified by image analysis of the axonal density of the nucleu s basalis projection to the somatosensory cortex visualized with acety lcholinesterase histochemistry. Pretreatment with 8-OH-DPAT-but not ip sapirone-1 h prior to NMDA infusion showed significant preservation of cortical cholinergic innervation in all doses tested. Furthermore, 8- OH-DPAT exhibited sustained efficacy under homeothermic conditions in which the body temperature was maintained at 36.8 +/- 0.1 degrees C. T hese data indicate that selective 5-HT1A receptor activation by 8-OH-D PAT protects against NMDA-induced excitotoxic neuronal damage, probabl y as a result of 5-HT1A receptor-mediated neuronal hyperpolarization. (C) 1998 Elsevier Science B.V. All rights reserved.