단기적과 장기적인 코카인으로 인한 Drd2-EGFP쥐의 행동적 생리학적 변화Behavioral and physiological alterations of Drd2-EGFP mice by acute and repeated exposure to cocaine
- 단기적과 장기적인 코카인으로 인한 Drd2-EGFP쥐의 행동적 생리학적 변화Behavioral and physiological alterations of Drd2-EGFP mice by acute and repeated exposure to cocaine
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- Drd1- and Drd2-EGFP BAC transgenic mice in which EGFP is driven by dopamine D1 (Drd1) and D2 receptor (Drd2) promoters have been widely used to define cell-type specific features and also pursue cellular correlates underlying addictive behaviors to drug of abuse. However, the usage of Drd2-EGFP mice, particularly for investigation of cocaine-induced neuroadaptaion has been challenged by the observation that Drd2-EGFP mice failed to exhibit addictive behaviors to cocaine. Thus, detailed analysis appears to be essential for behavioral and physiological traits that Drd2-EGFP mice have. In this study, we found that Drd2-EGFP homozygote mice showed hyper-sensitized responses to cocaine exposure earlier than heterozygote and wild-type mice did. In parallel, a single injection of cocaine was enough for decreasing excitability of Drd1-expressing neurons in the
homozygote mice, which differs from Drd2-EGFP heterozygote mice that resulted in a decrease in excitability only on repeated infusion of cocaine. Finally, we provide evidence that Drd2-EGFP heterozygote mice can be a reliable model system for addiction research whereas Drd2-EGFP homozygote mice exhibit higher behavioral sensitivity to cocaine, perhaps due to a drastic increase in D2R level and/or impaired clearance of ambient dopamine.
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