Increased expression of zif268 mRNA in rat retrosplenial cortex following administration of phencyclidine

Phencyclidine (PCP) has been shown to cause neurotoxicity in rat retrosplenial cortex following a single administration, although the precise mechanism underlying PCP-induced neurotoxicity is unclear. Using in situ hybridization and immunohistochemistry, we studied the effects of PCP on expression of immediate early gene zif268 mRNA and zif268 protein in the rat brain. High constitutive levels of zif268 mRNA and zif268 immunoreactivity were observed in the brain of control rats. Administration of PCP (12.5, 25 or 50 mg/kg, i.p., 6 h) caused marked induction of zif268 mRNA in the rat retrosplenial cortex, in a dose-dependent manner. However, the basal levels of zif268 mRNA in the other regions of cerebral cortex were decreased by administration of PCP. Emulsion-autoradiographical study suggested that marked expression of zif268 mRNA was observed in the layers III and IV of retrosplenial cortex where the neurotoxicity of PCP was detected. Furthermore, zif268 immunoreactivity in the layer IV of retrosplenial cortex was not changed by administration of PCP (25 mg/kg, i.p., 5 h), but that in the other layers of retrosplenial cortex was reduced by PCP. These results suggest that immediate early gene zif268 may, in part, play a role in the neurotoxicity of NMDA receptor antagonists such as PCP.