Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Neuroimage. 2010 Jan 15;49(2):1259-70. doi: 10.1016/j.neuroimage.2009.07.072. Epub 2009 Aug 12.
3, 4-Methylenedioxymethamphetamine (MDMA, "ecstasy") has toxic effects on serotonergic neurons in the brain. Our aim was to determine whether N,N-dimethyl-2-(2-amino-4-[(18)F]-fluorophenylthio) benzylamine (4-[(18)F]-ADAM; a serotonin transporter imaging agent) and micropositron emission tomography (micro-PET) can be used to examine in vivo the effect of fluoxetine on MDMA-induced loss of serotonin transporters in rat brain. Male Sprague-Dawley rats were injected with fluoxetine [1 dose, 5 mg/kg, subcutaneously (s.c.)] followed by MDMA (twice a day for 4 consecutive days, 10 mg/kg, s.c.). Micro-PET with 4-[(18)F]-ADAM was performed on days 4, 10, 17, 24, and 31. In addition, the time course of occupancy by fluoxetine at 4-[(18)F]-ADAM sites was measured. Specific 4-[(18)F]-ADAM uptake ratios (SURs) were calculated from the micro-PET imaging data for various brain regions. Immunohistochemistry was performed 7 days after the last micro-PET scan. From day 4 to day 31, SURs were markedly decreased (by approximately 55-75% compared to control values) in all brain regions in MDMA-treated rats. The effect of MDMA was markedly attenuated (approximately 30-50%) by fluoxetine. The fluoxetine-induced decrease in uptake in different brain regions was 40-75% at 90-min postinjection, and this decrease returned to baseline values in most brain regions by day 31. The distribution and intensity of serotonin transporter (SERT) immunostaining in the brain paralleled the PET imaging results, suggesting that a single dose of fluoxetine provides long-lasting protection against MDMA-induced loss of SERT and that such neuroprotection is detectable in vivo by 4-[(18)F]-ADAM micro-PET.
3,4-亚甲二氧基甲基苯丙胺（MDMA，“摇头丸”）对大脑中的 5-羟色胺能神经元有毒性作用。我们的目的是确定 N,N-二甲基-2-（2-氨基-4-[(18)F]-氟苯基硫代）苄胺（4-[(18)F]-ADAM；一种 5-羟色胺转运体成像剂）和微正电子发射断层扫描（micro-PET）是否可用于检测氟西汀对 MDMA 诱导的大鼠脑内 5-羟色胺转运体丧失的体内作用。雄性 Sprague-Dawley 大鼠皮下注射氟西汀[1 剂量，5mg/kg]，随后每天两次皮下注射 MDMA（连续 4 天，10mg/kg）。在第 4、10、17、24 和 31 天进行 4-[(18)F]-ADAM 的 micro-PET。此外，还测量了氟西汀在 4-[(18)F]-ADAM 部位的占据时间过程。从 micro-PET 成像数据中计算出各个脑区的特异性 4-[(18)F]-ADAM 摄取比（SUR）。免疫组织化学在最后一次 micro-PET 扫描后 7 天进行。从第 4 天到第 31 天，MDMA 处理的大鼠所有脑区的 SUR 明显降低（与对照值相比降低约 55-75%）。氟西汀明显减弱了 MDMA 的作用（约 30-50%）。不同脑区氟西汀诱导的摄取减少在注射后 90 分钟时为 40-75%，并且这种减少在大多数脑区在第 31 天恢复到基线值。脑内 5-羟色胺转运体（SERT）免疫染色的分布和强度与 PET 成像结果平行，表明单次剂量的氟西汀可提供对 MDMA 诱导的 SERT 丧失的长期保护，并且这种神经保护作用可通过 4-[(18)F]-ADAM micro-PET 进行体内检测。
