期刊
MOLECULAR PSYCHIATRY
卷 12, 期 8, 页码 756-766出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.mp.4001993
关键词
Nurr1 mutant mouse; phencyclidine; amphetamine; haloperidol; locomotion
The transcription factor Nurr1 (NR4A2) has been found to play a critical role in the development of midbrain dopaminergic neurons. Nurr1 heterozygous (+/-) male and female mice expressing 35-40% of normal levels of Nurr1 were generated and examined in animal models related to symptoms of schizophrenia. The Nurr1 (+/-) mice displayed hyperactivity in a novel environment, which persisted after administration of the dopamine-mimetic amphetamine and the N-methyl-D-aspartate receptor antagonist phencyclidine. The Nurrl (+/-) mice were deficient in the retention of emotional memory and showed an enhanced response to swim stress. In addition, Nurrl (+/-) male mice displayed a reduced dopamine turnover in the striatum and an enhanced dopamine turnover in the prefrontal cortex, while female mice showed an opposite pattern. These results show that Nurrl (+/-) mice display a pattern of behaviors indicative of potential relevance for symptoms of schizophrenia combined with a gender-specific abnormal dopamine transmission in the striatum and prefrontal cortex, respectively. This suggests that the Nurrl mutant mouse may be a potential animal model for studies on some of the behavioral and molecular mechanisms underlying schizophrenia.
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