Investigating Brain Dopamine Transporter in ADHD Rat Model Using 99mTc-TRODAT-1/SPECT

• Main Authors: Yeh, KuanYi, 葉冠毅
• Other Authors: Ma, KuoHsing
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/21194223198472236006

碩士 === 國防醫學院 === 生物及解剖學研究所 === 100 === Attention-Deficit/Hyperactivity Disorder (ADHD) is characterized by excessive inattention, hyperactivity, and impulsivity. Those symptoms were complicated for clinical therapy. While the levels of monoamine metabolite excreted in ADHD are often correlated, dopamine transporter/ dopaminergic abnormalities have been frequently found in striatum. The purposes of this study are to establish in vivo imaging techniques in rats, and then using the neuroimaging method to investigate the relationship between the dopamine transporter and ADHD. 99mTc-TRODAT-1/SPECT were used to imaging the ADHD rat. Previous data indicated that 99mTc- TRODAT-1 hardly penetrate rat blood brain barrier(BBB) and resulting in poorly striatial uptakes. We used mannitol to induce a temporary BBB disruption without causing brain damage to observe the 99mTc-TRODAT-1 uptakes in rat brains. That will address the possible pathophysiology and validity of 99mTc-TRODAT-1/SPECT imaging techniques in rats. Our data showed the 99mTc-TRODAT-1 SURs of the normal rats that pretreat mannitol is higher than those without mannitol. To establish ADHD model, the 6-OHDA was injected into the brain of neonatal rats(P3). The results of behavior test showed the 6-OHDA lesioned rat had higher activity than normal. In image results, the 99mTc-TRODAT-1 uptake in striatum of 6-OHDA lesioned rat was markly lower than those of control. Our results suggest that 99mTc-TRODAT-1 with mannitol may be a useful method in evaluating the change of DAT in rat and the expression of DAT are decreased in striatum of 6-OHDA lesioned rat. Our study provide useful information in developing the new drug, and have better methods of monitoring its therapeutic responses.