Increased binding of cortical and hippocampal group II metabotropic glutamate receptors in isolation-reared mice.
Post-weaning social isolation in rodents induces behavioral alterations, including hyperlocomotion, depression- and anxiety-like behaviors, aggression, and learning and memory deficits. These behavioral abnormalities may be related to the core symptoms in patients with neuropsychiatric disorders, such as schizophrenia and depression. In view of the recent studies that the group II metabotropic glutamate receptor (mGluR2/3) is involved in neuropsychiatric disorders, the present study examined the effect of isolation rearing on the binding of the mGluR2/3 antagonist [(3)H]LY341495 to mGluR2/3 in the mouse brain by in vitro autoradiography. The [(3)H]LY341495 binding in the prefrontal cortex, cerebral cortical layers I-III and hippocampus was significantly increased by rearing in social isolation while the binding in other brain regions was not altered. A saturation binding study of hippocampal membranes from isolation-reared mice revealed that the B(max) value increased significantly without any changes in the K(d) value. Moreover, the mGluR2/3 antagonist MGS0039 (1.0mg/kg, intraperitoneally) decreased the immobility time of isolation-reared mice in the forced swim test. These results suggest that isolation rearing causes an increase in mGluR2/3 densities in the prefrontal cortex and hippocampus and that the increased receptor function may contribute to pathogenic mechanisms for depression-like behavior of the isolation-reared mice.
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Toshiyuki
T
Kawasaki
Yukio
Y
Ago
Koji
K
Yano
Ryota
R
Araki
Yusuke
Y
Washida
Hirotaka
H
Onoe
Shigeyuki
S
Chaki
Atsuro
A
Nakazato
Hitoshi
H
Hashimoto
Akemichi
A
Baba
Kazuhiro
K
Takuma
Toshio
T
Matsuda
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D017397:Prefrontal Cortex / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012934:Social Isolation / Q000523:psychology; D014966:Xanthenes / Q000378:metabolism
D000596:Amino Acids; C114624:LY 341495; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3