Alterations in NMDA receptor subunit levels in the brain regions of rats chronically administered typical or atypical antipsychotic drugs.
It has been hypothesized that glutamatergic neurotransmission is related to the therapeutic effect of antipsychotic drugs. To test this hypothesis, we measured by use of the Western blot technique the polypeptide levels of NMDA receptor subunits, that is, NMDAR1, 2A, 2B, and 2C, in several regions of the rat brain after chronic treatment with haloperidol (HPD) or clozapine (CLZ). Each rat was intraperitoneally injected with HPD or CLZ at 10:00 h daily for 14 days. The brain regions examined were frontal cortex, striatum, nucleus accumbens, hippocampus, and cerebellum. Decreases in the polypeptide level of NMDAR2B were seen in hippocampus (but not in other brain regions) following the treatment with HPD or CLZ. Altered levels in NMDAR1-, 2A-, and 2C were not detected in any brain regions examined. We infer that an alteration in NMDAR2B in hippocampus is related to therapeutic effects of antipsychotic drugs.
Hanaoka
Tadahito
T
Department of Neuropsychiatry, Osaka Medical College, 2-7 Daigakumachi, Takatsuki-City, Osaka 569-8686, Japan.
Toyoda
Hirotaka
H
Mizuno
Takafumi
T
Kikuyama
Hiroki
H
Morimoto
Kazushige
K
Takahata
Ryuichi
R
Matsumura
Hitoshi
H
Yoneda
Hiroshi
H
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D021122:Protein Subunits / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*
D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor