The role of sigma receptors in the induction of heat shock protein (HSP)-70 by non-competitive N-methyl-Daspartate (NMDA) receptor antagonists (+)-MK-801 (dizocilpine) and phencyclidine (PCP) was studied. HSP-70 is induced in the posterior cingulate and retrosplenial cortex of rat brain 24 hours after a single administration of dizocilpine (1 mg/kg) or PCP (50 mg/kg). The induction of heat shock protein HSP-70 by dizocilpine or PCP was attenuated partially by pre-treatment with the antipsychotic drug haloperidol (3 mg/kg, i.p., 15 minutes previously). However, pre-treatment with high potent and selective sigma receptor ligands, 4-phenyl-4-(1-phenylbutyl)piperidine (4-PPBP, 3 mg/kg, i.p., 15 minutes previously) and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride) (NE-100, 3 mg/kg, i.p., 15 minutes previously) did not alter the induction of HSP-70 by dizocilpine or PCP. These findings suggest that sigma receptors may not play a significant role in the induction of HSP-70 by non-competitive NMDA receptor antagonists dizocilpine and PCP, and that protective effects of haloperidol on induction of HSP-70 protein by dizocilpine or PCP may be due to other effect(s) except sigma receptors.