Abstract
The dopamine transporter (DAT) plays a pivotal role in maintaining optimal dopamine signaling. DAT-overactivity has been linked to various neuropsychiatric disorders yet so far the direct pathological consequences of it has not been fully assessed. We here generated a transgenic rat model that via pronuclear microinjection overexpresses the DAT gene. Our results demonstrate that DAT-overexpression induces multiple neurobiological effects that exceeded the expected alterations in the corticostriatal dopamine system. Furthermore, transgenic rats specifically exhibited behavioral and pharmaco-therapeutic profiles phenotypic of repetitive disorders. Together our findings suggest that the DAT rat model will constitute a valuable tool for further investigations into the pathological influence of DAT overexpression on neural systems relevant to neuropsychiatric disorders.
Highlights
On this basis we created a transgenic rat model that via pronuclear microinjection overexpresses the dopamine transporter (DAT) gene (Fig. 1)
Western blot and quantitative real time PCR (qPCR) were performed in order to assess the protein and mRNA expression levels of the dopamine transporter (DAT). qPCR was conducted to assess mRNA expression levels of the dopamine receptor 1 (DRD1), and dopamine receptor 2 (DRD2)
Our results show that overexpression of the DAT induces multiple neurobiological and behavioral deficits that have been observed in repetitive disorders
Summary
With regards to metabolites and turnorver, DAT-tg rats exhibited increased DOPAC contents and dopamine turnover (DOPAC/dopamine) in the mPFC (DOPAC: T = 4.255, p = 0.000; turnover: T = 2.916, p = 0.011), OFC (T = 3.225, p = 0.006; turnover: T = 13.467, p = 0.000), Nacc (T = 4.391, p = 0.000; turnover: T = 7.542, p = 0.000), CPu (T = 9.134, p = 0.000; turnover: T = 19.314, p = 0.000), GP (T = 6.177, p = 0.000; turnover: T = 7.417, p = 0.000), Hipp (T = 5.884, p = 0.000; turnover: T = 1.35, p = 0.022), Thal (T = 4.009, 0.001; turnover: T = 1.505, p = 0.001) and STN (T = 4.503, p = 0.000; turnover: T = 2.962, p = 0.010) (Fig. 3a–c).
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