TY - JOUR
T1 - Effects of single and repeated phencyclidine administration on the expression of metabotropic glutamate receptor subtype mRNAs in rat brain
AU - Abe, Shuzo
AU - Suzuki, Toshihito
AU - Ito, Takehiko
AU - Yamaguchi, Mika
AU - Baba, Atsuomi
AU - Hori, Takafumi
AU - Kurita, Hirofumi
AU - Shiraishi, Hiroyasu
AU - Okado, Nobuo
N1 - Funding Information:
This study was supported in part by a Grant-in-Aid for Scientific Research(C) 08671072 from the Ministry of Education, Science and Culture to TS.
PY - 2001
Y1 - 2001
N2 - Recent animal studies regarding phencyclidine (PCP), which induces psychotic symptoms in humans, have suggested that group II metabotropic glutamate receptors (mGluRs) represent a novel target for the treatment of PCP psychosis. In the present study, we used in situ hybridization to investigate the gene expressions of the mGluR 1-5 subtypes following single and repeated administration of PCP in rats. A single administration of PCP (7.5mg/kg, i.p.,) resulted in a significant decrease in the mGluR5 mRNA expression of group I mGluR in the subcortical regions (thalamus (-15%), central gray (-23%), inferior colliculus (-23%), and nucleus accumbens (-10%)) and hippocampal formation (CA1 (-14%), CA2 (-15%), CA3 (-18%), and dentate gyrus (-18%)). After repeated PCP administration for 14 days, the mGluR2 mRNA expression of group II mGluR in the anterior cingulate cortex (-23%) and the mGluR4 mRNA expression of group III mGluR in the cortical regions (parietal (-11%), temporal (-13%) and entorhinal cortices (-18%)), the caudate putamen (-12%), thalamus (-17%), and subiculum (-25%) were significantly decreased. These results indicate that PCP affects not only group II mGluR but also group I and III of mGluR, and it is of particular interest that mGluR2 subtype is involved in a development of behavioral abnormality following repeated PCP administration. Single and repeated administrations of PCP independently regulate the expression of mGluR subtypes of mRNA in the brain.
AB - Recent animal studies regarding phencyclidine (PCP), which induces psychotic symptoms in humans, have suggested that group II metabotropic glutamate receptors (mGluRs) represent a novel target for the treatment of PCP psychosis. In the present study, we used in situ hybridization to investigate the gene expressions of the mGluR 1-5 subtypes following single and repeated administration of PCP in rats. A single administration of PCP (7.5mg/kg, i.p.,) resulted in a significant decrease in the mGluR5 mRNA expression of group I mGluR in the subcortical regions (thalamus (-15%), central gray (-23%), inferior colliculus (-23%), and nucleus accumbens (-10%)) and hippocampal formation (CA1 (-14%), CA2 (-15%), CA3 (-18%), and dentate gyrus (-18%)). After repeated PCP administration for 14 days, the mGluR2 mRNA expression of group II mGluR in the anterior cingulate cortex (-23%) and the mGluR4 mRNA expression of group III mGluR in the cortical regions (parietal (-11%), temporal (-13%) and entorhinal cortices (-18%)), the caudate putamen (-12%), thalamus (-17%), and subiculum (-25%) were significantly decreased. These results indicate that PCP affects not only group II mGluR but also group I and III of mGluR, and it is of particular interest that mGluR2 subtype is involved in a development of behavioral abnormality following repeated PCP administration. Single and repeated administrations of PCP independently regulate the expression of mGluR subtypes of mRNA in the brain.
KW - Glutamate
KW - In situ hybridization
KW - Metabotropic glutamate receptor
KW - NMDA antagonist
KW - Phencyclidine
KW - Schizophrenia
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U2 - 10.1016/S0893-133X(00)00250-5
DO - 10.1016/S0893-133X(00)00250-5
M3 - Article
C2 - 11425501
AN - SCOPUS:0034979643
SN - 0893-133X
VL - 25
SP - 173
EP - 184
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 2
ER -
