Generation and characterization of hD₅ and C-terminal Mutant hD_5m transgenic rats

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• 作者：Zhiliang Xu^a ; ^b ; ¹ ; Suzhen Dong^a ; ^b ; ¹ ; Dan Du^b ; Nan Jiang^b ; Peiqua Sun^c ; Huikun Wang^c ; Liang Yin^b ; Xuliang Zhang^b ; Xiaohua Cao^b ; Xuechu Zhen^c ; Yinghe Hu^a ; ^{yhu@brain.ecnu.edu.cn}
• 关键词：D1-like dopamine receptor ; Learning and memory ; Transgenic rat ; LTP
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：11 April, 2012
• 卷：1448
• 期：Complete
• 页码：27-41
• 文件大小：1478 K

摘要

Dopamine D₁-like receptors play important roles in many brain activities such as cognition and emotion. We have generated human hD₅ and mutant human hD₅ (hD_5m) transgenic rats. The C-terminal juxtamembrane domain of mutant hD₅ was identical to that of hD5 pseudogenes. The transgenes were driven by the CAMKII promoter that led the expression mainly in the cerebral cortex and hippocampus. We have used different dopamine receptor agonists to compare the pharmacological profiles of the human hD₅ and hD_5m receptors. The results showed that they exhibited distinct pharmacological properties. Our results of pharmacological studies indicated that the C-terminal of D₅ receptor could play important roles in agonist binding affinity. Hippocampal long-term potentiation (LTP) evoked by tetanic stimulation was significantly reduced in both transgenic rats. In addition, we found that the overexpression of dopamine hD₅ and hD_5m receptors in the rat brain resulted in memory impairments. Interestingly, an atypical D₁-like receptor agonist, SKF83959, could induce anxiety in hD_5m receptor transgenic rats but had no effect on the anxiety-like behavior in D₅ receptor transgenic and wild-type rats.