YM90K, a selective-amino-3-hydroxy5-methyl-4-isoxazole propionate (AMPA) receptor antagonist, prevents induction of heat shock protein HSP -70 and hsp -70 mRNA in rat retrosplenial cortex by phencyclidine.

Abstract:

:The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist such as an abused drug phencyclidine (PCP) causes the induction of heat shock protein HSP-70, a sensitive marker of neuronal injury, in the retrosplenial cortex of rat brain. The present study was undertaken to examine the role of a -amino-3- hydroxy-5-methyl-4-isoxazole propionate (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 immunoreactivity was detected in the vehicle-treated group. Pretreatment with a potent 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 of PCP (50 mg/kg, i.p) caused marked expression of hsp-70 mRNA in the retrosplenial cortex of rat brain, whereas the expression of hsp-70 mRNA was NOT found in the vehicle-treated group. Pretreatment with YM90K (1, 3 or 10 mg/kg, i p; 15 min) also inhibited the expression of hsp-70 mRNA by PCP (50 mg/kg), in a dose-dependent manner. These results suggest 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 cortex of rat brain by non-competitive NMDA receptor antagonists such as PCP.

journal_name

Addict Biol

journal_title

Addiction biology

authors

Narita N,Hashimoto K,Tomitaka S,Minabe Y,Yamazaki K

doi

10.1080/13556219772859

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

47-56

issue

1

eissn

1355-6215

issn

1369-1600

journal_volume

2

pub_type

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