P.1.j.022 A dopamine D1 agonist improved ketamineinduced spatial working memory dysfunction in common marmosets

Abstract

Using the RNA arbitrarily-primed PCR and the competitive RT-PCR, we have isolated the neocortical transcripts that are upregulated and unchanged in the adult and infant rats, respectively, after a systemic injection of an N-methyl-d-aspartate (NMDA) receptor antagonist phencyclidine (PCP), and found them identical to the synapse-associated protein-97 (SAP97) gene mRNAs. The upregulation of the SAP97 transcripts in the adult neocortex after the acute PCP injection was mimicked by another NMDA antagonist, dizocilpine, but not by the indirect dopamine agonists, methamphetamine and cocaine, a selective D1 receptor antagonist SCH23390, a D2 receptor-preferring antagonist haloperidol and a GABAergic anesthetic pentobarbital. Moreover, the pretreatment with a typical antipsychotic haloperidol failed to antagonize the increased neocortical SAP97 gene expression by PCP. These findings suggest that SAP97 might be involved in the molecular basis of the development-dependent onset of the non-dopaminergic symptoms seen in schizophrenia and the schizophrenia-like psychosis induced by NMDA receptor blocking.