DNQX inhibits phencyclidine (PCP) and ketamine induction of the hsp70 heat shock gene in the rat cingulate and retrosplenial cortex

Abstract

Phencyclidine (PCP) and ketamine are known to block NMDA receptor mediated excitotoxicity by non-competitively blocking the NMDA receptor calcium channel. PCP and ketamine have the paradoxical effect of also inducing the heat shock gene, hsp70, in the cingulate and retrosplenial cortex of the rat. The present study shows that DNQX, a specific AMPA receptor antagonist, given as either a 5 mg/kg or 10 mg/kg intraperitoneal dose or into the lateral cerebral ventricle (5 μl of 0.5 mg/ml) significantly diminished PCP (40 mg/kg) and ketamine (80, 100, 120 mg/kg) hsp70 induction in the posterior cingulate and retrosplenial cortex. The most dramatic decrease of hsp70 induction was seen with the intraventricular dose of DNQX. Present findings show that the AMPA receptor has a role in PCP/ketamine induction of hsp70 in the cortex. DNQX inhibition of PCP/ketamine hsp70 induction was likely related to AMPA receptor antagonism which prevented excess calcium influx via voltage-gated calcium channels.