Region specific regulation of NR1 in rhesus monkeys following chronic antipsychotic drug administration.
BACKGROUND
Altered NMDA receptor subunit protein levels have been reported in various regions of the schizophrenic brain; however, chronic antipsychotic administration in schizophrenic subjects may confound interpretation.


METHODS
The effects of chronic antipsychotic drug administration (haloperidol and clozapine) on protein levels of NR1, NR2A and NR2B proteins were evaluated in the nucleus accumbens (NAc), putamen (PUT), dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus (STG), and entorhinal cortex (EC) of rhesus monkeys using Western blot analysis.


RESULTS
Haloperidol administration significantly decreased NR1 expression in the DLPFC. In contrast, NR2B expression was not affected by antipsychotic administration in any brain region examined. NR2A was not reliably detected in any of the brain regions.


CONCLUSIONS
Results indicate that the NR1 subunit in the DLPFC may be a substrate for antipsychotic action and that glutamatergic hypofunction in the DLPFC commonly associated with cognitive dysfunction in schizophrenia may be associated with haloperidol administration.
O'Connor
Joann A
JA
Yerkes National Primate Research Center, Neuroscience Division, Atlanta, Georgia, USA.
Hasenkamp
Wendy
W
Horman
Brian M
BM
Muly
E Chris
EC
Hemby
Scott E
SE
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects*; D003024:Clozapine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D008253:Macaca mulatta; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D014150:Antipsychotic Agents; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D003024:Clozapine; D006220:Haloperidol