Effect of psychostimulants on pharmacokinetics of [18F]FDOPA in rats by quantitative autoradiography

• Main Authors: Li-Chung Hwang, 黃立宗
• Other Authors: Jeng-Jong Hwang
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/13947738778101906795

碩士 === 國立陽明大學 === 放射醫學科學研究所 === 92 === The effects and the mechanisms of the several psychostimulants on the dopaminergic neurosystem have been studied. 6-[18F]-fluoro-L-DOPA ([18F]FDOPA), a radiopharmaceutical, has been used to detect the biochemical activities of dopaminergic neurons. In this study, the effects of acute administration of psychostimulants on dopamine neuron system of Sprague-Dawley rat brain before or after [18F]FDOPA injection were investigated using quantitative autoradiography (QARG) in combination with micro positron emission tomography (microPET). Male Sprague-Dawley (SD) rats (250±25 grams) were used in this study. All rats were given carbidopa (28 mg/kg) by gavage 1 hr prior to intravenous injection (i.v.) of [18F]FDOPA (37 MBq). The rats were sacrificed at 0.25, 0.5, 1 and 2 hrs after [18F]FDOPA injection to acquire the striatum to frontal cortex (S/FC) ratio by microautoradiography and QARG. MicroPET imaging was also performed at the same time points. In the control group, both QARG and microPET showed that the S/FC ratio at 2 hours after [18F]FDOPA injection was the highest. In addition, the highest density of silver grams was also found in the striatum 2 hours after [18F]FDOPA injection from microautoradiography. For drug post-treated groups, rats were administrated with cocaine (5-25 mg/kg, i.v.), methamphetamine (5-50 mg/kg, i.v.) or ketamine (5-60 mg/kg, i.p.) 1.5 hours after [18F]FDOPA injection. And all rats were sacrificed with chloroform 30 min after drug administration. The striatum to frontal cortex ratio at 2 hours in cocaine (20 mg/kg), methamphetamine (40 mg/kg) and ketamine (40 mg/kg) post-treated group were significantly (P < 0.001) reduced to 52%, 39% and 27% of the control, respectively, assayed by QARG. In pre-treated group, the striatum to frontal cortex ratio at 2 hours in cocaine (20 mg/kg), methamphetamine (40 mg/kg) and ketamine (40 mg/kg) were reduced to 60%, 62% and 73% of the control. The effect of psychostimulants on [18F]FDOPA uptake all showed the dose-dependent manner at the lower dose range. At high dose range (> or = 40 mg/kg), ketamine showed the highest inhibition capability following by methamphetamine and cocaine. High resolution (25 μm) quantitative autoradiography combined with microPET (resolution 1-2 mm) is very valuable for the evaluation of the effect of the psychostimulants on the biosynthesis/metabolism, neurotransporter or neuroreceptor. Quantitative autoradiography is not only good for the assay of the uptake ratio in pharmacokinetics, but also for the calculation of radioactivity in various regions of the brain.