NMDA RECEPTORS MEDIATE HEAT-SHOCK PROTEIN INDUCTION IN THE MOUSE-BRAIN FOLLOWING ADMINISTRATION OF THE IBOTENIC ACID ANALOG AMAA

Expression of inducible heat shock protein-70 (HSP-70) and hsp-70 mRNA were studied in the adult mouse brain following systemic administrati on of the ibotenic acid analogue (+/-)-2-amino-3-hydroxy-5-methyl-4-is oxazoleacetic acid (AMAA), which is a potent N-methyl-D-aspartate (NMD A) agonist. At the dose of 20 mg/kg, AMAA produced excitatory behaviou rs in adult mice but overt convulsions were not seen. This treatment d id not result in any detectable morphological brain damage at 4 days f ollowing administration. At 2.5 h and 5 h following treatment inductio n of hsp-70 mRNA expression was found in the pyramidal cell layers of CA1 and, to a lesser extent, CA3 fields of hippocampal Ammon's horn, a mygdala, olfactory lobes, tenia tecta, hypothalamic nuclei and a super ficial layer of cingulate, frontal and retrosplenial cortices. The pre sence of HSP-70 was detected by immunohistochemistry at 24 h following drug administration in those regions previously showing hsp-70 mRNA i nduction. AMAA-induced hsp-70 mRNA expression was prevented by pre-tre atment with the non-competitive NMDA antagonist MK-801. These results suggest that NMDA receptors are involved in the stress response induce d by AMAA.