YM90K, A SELECTIVE ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONATE (AMPA) RECEPTOR ANTAGONIST, PREVENTS INDUCTION OF HEAT-SHOCK PROTEIN HSP-70 AND HSP-70 MESSENGER-RNA IN RAT RETROSPLENIAL CORTEX BY PHENCYCLIDINE

The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist su ch as an abused drug phencyclidine (PCP) causes the induction of heat shock protein HSP-70, a sensitive marker of neuronal injury, in the re trosplenial cortex of rat brain. The present study was undertaken to e xamine the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propiona te (AMPA) receptor in the expression of heat shock protein HSP-70 and hsp-70 mRNA in the retrosplenial cortex by PCP. Administration of PCP (50 mg/kg, i.p.) caused the induction of heat shock protein HSP-70 in the retrosplenial cortex of rat brain, whereas no HSP-70 immunoreactiv ity was detected in the vehicle-treated group. Pretreatment with a pot ent and selective AMPA receptor antagonist YM90K (1, 3 or 10 mg/kg, i. p; 15 min) inhibited in a dose dependent manner, the induction of heat shock protein HSP-70 by PCP (50 mg/kg). Furthermore, administration o f PCP (50 mg/kg, i.p) caused marked expression of hsp-70 mRNA in the r etrosplenial cortex of rat brain, whereas the expression of hsp-70 mRN A was NOT found in the vehicle-treated group. Pretreatment with YM90K (I, 3 or 10 mg/kg, ip; 15 min) also inhibited the expression of hsp-70 mRNA by PCP (50 mg/kg), in a dose-dependent manner These results sugg est that AMPA receptor may play a role in the expression of heat shock protein HSP-70 and heat shock gene hsp-70 mRNA in the retrosplenial c ortex of rat brain by non-competitive NMDA receptor antagonists such a s PCP.