Effects of single and repeated phencyclidine administration on the expression of metabotropic glutamate receptor subtype mRNAs in rat brain.
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.
Abe
S
S
Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Suzuki
T
T
Ito
T
T
Yamaguchi
M
M
Baba
A
A
Hori
T
T
Kurita
H
H
Shiraishi
H
H
Okado
N
N
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010622:Phencyclidine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis*; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; D010622:Phencyclidine