Differential regulation of hippocampal AMPA and kainate receptor subunit expression by haloperidol and clozapine.
Dopamine-glutamate interactions within discrete neural circuits are increasingly recognized as potential substrates for dysregulation in schizophrenia, and as a result, potential targets for pharmacological intervention in this illness. We examined the regulation, by haloperidol (2 mg kg-1 day-1) and clozapine (20 mg kg-1 day-1), of the mRNAs encoding the four AMPA receptor subunits (gluR1-gluR4), three low-affinity kainate receptor subunits (gluR5-gluR7), and two high-affinity kainate subunits (KA1 and KA2) in the rat hippocampal formation and associated entorhinal cortex. A complex and differential pattern of AMPA and kainate subunit mRNA regulation by clozapine and haloperidol was observed in this study. Both drugs caused significant alterations of most of these mRNAs, but in a heterogeneous and region-specific fashion. These data suggest that these antipsychotic drugs alter the expression of the genes encoding the subunits that express ionotropic glutamate receptors. Given the importance of glutamatergic mechanisms and the hippocampal formation in schizophrenia, these data suggest a potential substrate for neurotransmitter dysregulation in this illness, as well as a potential target for therapeutic intervention.
Meador-Woodruff
J H
JH
Mental Health Research Institute, University of Michigan, Ann Arbor 48109-0720, USA.
King
R E
RE
Damask
S P
SP
Bovenkerk
K A
KA
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D018728:Entorhinal Cortex / Q000737:chemistry / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000737:chemistry* / Q000187:drug effects; D017403:In Situ Hybridization; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000737:chemistry / Q000187:drug effects / Q000235:genetics*; D018092:Kainic Acid Receptors / Q000737:chemistry / Q000187:drug effects / Q000235:genetics*
D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol; D012333:RNA, Messenger; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors