TY - JOUR
T1 - Behavioral abnormalities and dopamine reductions in sdy mutant mice with a deletion in Dtnbp1, a susceptibility gene for schizophrenia
AU - Hattori, Satoko
AU - Murotani, Tomotaka
AU - Matsuzaki, Shinsuke
AU - Ishizuka, Tomoko
AU - Kumamoto, Natsuko
AU - Takeda, Masatoshi
AU - Tohyama, Masaya
AU - Yamatodani, Atsushi
AU - Kunugi, Hiroshi
AU - Hashimoto, Ryota
N1 - Funding Information:
This work was supported in part by the Japanese Ministry of Education, Culture, Sports, Science and Technology, CREST of JST, and Grant-in-Aid for Scientific Research on Priority Areas -Research on Pathomechanisms of Brain Disorders- from the MEXT (18023045).
PY - 2008/8/22
Y1 - 2008/8/22
N2 - Genetic susceptibility plays an important role in the pathogenesis of schizophrenia. Genetic evidence for an association between the dysbindin-1 gene (DTNBP1: dystrobrevin binding protein 1) and schizophrenia has been repeatedly reported in various populations worldwide. Thus, we performed behavioral analyses on homozygous sandy (sdy) mice, which lack dysbindin-1 owing to a deletion in the Dtnbp1 gene. Our results showed that sdy mice were less active and spent less time in the center of an open field apparatus. Consistent with the latter observation, sdy mice also displayed evidence of heightened anxiety-like response and deficits in social interaction. Compared to wild-type mice, sdy mice displayed lower levels of dopamine, but not glutamate, in the cerebral cortex, hippocampus, and hypothalamus. These findings indicate that sdy mice display a number of behavioral abnormalities associated with schizophrenia and suggest that these abnormalities may be mediated by reductions in forebrain dopamine transmission.
AB - Genetic susceptibility plays an important role in the pathogenesis of schizophrenia. Genetic evidence for an association between the dysbindin-1 gene (DTNBP1: dystrobrevin binding protein 1) and schizophrenia has been repeatedly reported in various populations worldwide. Thus, we performed behavioral analyses on homozygous sandy (sdy) mice, which lack dysbindin-1 owing to a deletion in the Dtnbp1 gene. Our results showed that sdy mice were less active and spent less time in the center of an open field apparatus. Consistent with the latter observation, sdy mice also displayed evidence of heightened anxiety-like response and deficits in social interaction. Compared to wild-type mice, sdy mice displayed lower levels of dopamine, but not glutamate, in the cerebral cortex, hippocampus, and hypothalamus. These findings indicate that sdy mice display a number of behavioral abnormalities associated with schizophrenia and suggest that these abnormalities may be mediated by reductions in forebrain dopamine transmission.
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U2 - 10.1016/j.bbrc.2008.06.016
DO - 10.1016/j.bbrc.2008.06.016
M3 - Article
C2 - 18555792
AN - SCOPUS:46049086735
SN - 0006-291X
VL - 373
SP - 298
EP - 302
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -