社團法人臺灣臨床藥學會

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【原著】放射性藥物探討搖頭丸誘發急性高熱反應與慢性血清素神經元毒性之造影研究
Study on MDMA-Induced Acute Hyperthermia and Long-Term Serotonergic Neurotoxicity Using Radioligand Imaging Technique
搖頭丸、棕色脂肪組織、高熱、血清素轉運體、正子斷層造影、MDMA, Brown Adipose Tissue, Hyperthermia, Serotonin Transporter, Positron Emission Tomography
施睿琥Jui-Hu Shih1.2.3 、林揚奕Yang-Yi Lin3 、李宜勳I-Hsun Li11.2.3
1三軍總醫院臨床藥學部 、2國防醫學院醫學科學研究所 、3國防醫學院藥學研究所
目的:許多研究已證實3,4-methylenedioxymethamphetamine (MDMA) 可藉由棕色脂肪組織活化誘導急性高熱反應,亦會對腦中血清素系統產生持久性的變化,包括血清素轉運體密度降低。然而,截至目前為止並無相關研究運用正子造影技術探討MDMA 誘發之高熱與血清素神經元毒性之關聯性。
方法:將雄性大鼠皮下注射生理食鹽水或MDMA (10 mg/kg),每日施打二次,連續四天。於施打第一劑生理食鹽水或MDMA 後1 小時,進行[18F]-FDG 正子斷層造影以探討MDMA 於急性期之棕色脂肪組織活化程度,並於給藥後2 小時測量其肛溫變化;另外於連續四天給藥後之兩週,進行4-[18F]-ADAM 正子斷層造影以探討MDMA 於慢性期血清素神經元受損程度之影響。
結果:[18F]-FDG 正子斷層造影結果顯示,MDMA 組別之頸部與肩胛骨間棕色脂肪組織活化,分別為控制組之4.3 與5.6 倍;肛溫亦增加1.8°C。4-[18F]-ADAM 正子斷層造影結果發現,MDMA 組別與控制組別相比,各腦區之血清素轉運體密度下降幅度約25.2 ~ 60.2% 且達統計之顯著差異。
結論:本研究證實MDMA可直接活化頸部與肩胛骨間之棕色脂肪組織,導致體溫顯著上升,進而產生慢性血清素神經元之損傷。
 
Objective: Numerous studies have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA)produces acute hyperthermia via the activation of brown adipose tissue and long-lasting changes to the serotonergic system, including decreases in the density of the serotonin transporter.However, to date, there has been no research to explore the relationship between MDMAinduced hyperthermia and serotonergic neurotoxicity using the nuclear imaging technique of positron emission tomography (PET).
Methods: Rats were treated with saline or MDMA (10 mg/kg, s.c.) twice daily for 4 consecutive days. To evaluate the acute effects of MDMA, PET imaging with [18F]-FDG for the assessment of brown adipose tissue (BAT) and rectal temperature were measured at one hour and two hours after the first MDMA dose, respectively. To evaluate the long-term effects of MDMA on serotonergic neurotoxicity, 4-[18F]-ADAM imaging was measured two weeks after drug treatment.
Results: The data of PET imaging showed that the extent of [18F]-FDG uptake of cervical and interscapular BAT in rats treated with MDMA were 4.3-fold and 5.6-fold higher than that in rats treated with saline, respectively. Rectal temperature was found to increase by approximately 1.8°C in the MDMA group in comparison with the control group. Besides, in the MDMA group, the densities of serotonin transporters in the various brain regions examined were significantly reduced, by 25.2% to 60.2%, relative to those in the control group.
Conclusions: These results suggest that MDMA-induced hyperthermia is a consequence of BAT activation,contributing to long-term serotonergic neurotoxicity.
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