Biodistributions of [123I] ADAM in the Brain of Hemiparkinsonian Rats

• Main Authors: Hui-Ling,Huang, 黃惠伶
• Other Authors: Jiang-Chuan, Liu
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/89730871483160934480

碩士 === 國防醫學院 === 生物及解剖學研究所 === 91 === Serotonin transporters (SERT) are target-sites for many antidepressants. Most reviewers acknowledge that there is a great demand for a highly selective SERT radioligand for SPECT. A radioligand for SPECT imaging with high selectivity for SERT would make it possible to monitor at-risk individuals with depression. However, no such radioligand is currently available for routine SPECT imaging. Recently, a highly selective radioligand, ADAM(2-((2-（(dimethylamino)methyl）)phenyl)thio)-5-iodophenylamine) was developed. Recent reports of [123I]ADAM for SPECT imaging in vivo showed its prominent uptake in several brain regions, which parallelled to known SERT areas and suggested that the [123I]ADAM may be useful for SPECT imaging of SERT binding sites in the human brain. In this study, we investigated the biodistributions of [123I]ADAM in brains of hemiparkinsonian rats and examined if the serotonergic system would be changed. At two hours after [123I]ADAM injection, the animals were sacrificed and the autoradiography was performed. In normal rats, there are high uptakes of [123I]ADAM in the hippocampus, hypothalamus, striatum, olfactory tubercle, substantia nigra, dorsal raphe, median raphe, and thalamus, as in areas possessing known SERT. A hemiparkinsonisonisum was induced by injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle of rats. Two weeks later, methamphetamine-induced rotation behavior was evaluated. We choose three rats that performed drug-induced rotation over 300 circles. We also examined dopaminergic neurons in hemiparkinsonian rats by tyrosine hydroxylase immunohistochemistry which showed decreased dopaminergic neurons in the substantia nigra of hemiparkinsonian rats. The autoradiographical images also demonstrated that the [123I]ADAM uptakes in the hippocampus, hypothalamus, striatum, olfactory tubercle, dorsal raphe, median raphe, and thalamus of hemiparkinsonian rats were significantly lower than those of normal rats. In conclusion, we proposed that the novel ligand [123I]ADAM can be highly selective for SERT. Through this high selective radioligand [123I]ADAM, a significant decreased the serotonin transporters in several brain tissues was found in hemiparkinsonian rats.