Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan.
Department of Nuclear Medicine, Tri-Service General Hospital, Taipei 114, Taiwan.
Int J Mol Sci. 2022 Jun 24;23(13):7035. doi: 10.3390/ijms23137035.
Numerous studies have confirmed that 3,4-Methylenedioxymethamphetamine (MDMA) produces long-lasting changes to the density of the serotonin reuptake transporter (SERT). Amitriptyline (AMI) has been shown to exert neuroprotective properties in neuropathologic injury. Here, we used a SERT-specific radionuclide, 4-[F]-ADAM, to assess the longitudinal alterations in SERT binding and evaluate the synergistic neuroprotective effect of AMI in a rat MDMA model. In response to MDMA treatment regimens, SERT binding was significantly reduced in rat brains. Region-specific recovery rate (normalized to baseline) in the MDMA group at day 14 was 71.29% ± 3.21%, and progressively increased to 90.90% ± 7.63% at day 35. AMI dramatically increased SERT binding in all brain regions, enhancing average ~18% recovery rate at day 14 when compared with the MDMA group. The immunochemical staining revealed that AMI markedly increased the serotonergic fiber density in the cingulate and thalamus after MDMA-induction, and confirmed the PET findings. Using in vivo longitudinal PET imaging, we demonstrated that SERT recovery was positively correlated with the duration of MDMA abstinence, implying that lower SERT densities in MDMA-induced rats reflected neurotoxic effects and were (varied) region-specific and reversible. AMI globally accelerated the recovery rate of SERT binding and increased SERT fiber density with possible neuroprotective effects.
许多研究已经证实，3,4-亚甲二氧基甲基苯丙胺（MDMA）会对 5-羟色胺再摄取转运体（SERT）的密度产生持久的变化。阿米替林（AMI）已被证明在神经病理损伤中具有神经保护作用。在这里，我们使用 SERT 特异性放射性核素 4-[F]-ADAM 来评估 SERT 结合的纵向变化，并评估 AMI 在大鼠 MDMA 模型中的协同神经保护作用。在 MDMA 治疗方案的作用下，大鼠大脑中的 SERT 结合显著减少。在 MDMA 组中，14 天时的区域特异性恢复率（相对于基线归一化）为 71.29%±3.21%，并在 35 天时逐渐增加到 90.90%±7.63%。AMI 显著增加了所有脑区的 SERT 结合，与 MDMA 组相比，在 14 天时平均恢复率提高了约 18%。免疫化学染色显示，AMI 明显增加了中扣带回和丘脑的 5-羟色胺能纤维密度，证实了 PET 发现。通过体内纵向 PET 成像，我们证明 SERT 恢复与 MDMA 戒断时间的长短呈正相关，这表明 MDMA 诱导大鼠中 SERT 密度降低反映了神经毒性作用，并且是（变化）区域特异性和可逆转的。AMI 全面加速了 SERT 结合的恢复速度，并增加了 SERT 纤维密度，具有可能的神经保护作用。
