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Article

Amitriptyline Accelerates SERT Binding Recovery in a Rat 3,4-Methylenedioxymethamphetamine (MDMA) Model: In Vivo 4-[18F]-ADAM PET Imaging

1
Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan
2
Department of Nuclear Medicine, Tri-Service General Hospital, Taipei 114, Taiwan
3
Department of Nursing, Hsin-Sheng College of Medical Care and Management, Taoyuan 325, Taiwan
4
Department of Nuclear Medicine, Cheng-Hsin General Hospital, Taipei 112, Taiwan
5
Brain Research Center, National Yang Ming Chaio Tung University, Taipei 112, Taiwan
6
Radiomedix, Inc., Houston, TX 77042, USA
7
School of Medicine, National Defense Medical Center, Taipei 110, Taiwan
8
Department of Biology and Anatomy, National Defense Medi Center, Taipei 110, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Matteo Marti, Liana Fattore, Carlo Locatelli and Monia Lenzi
Int. J. Mol. Sci. 2022, 23(13), 7035; https://doi.org/10.3390/ijms23137035
Received: 1 June 2022 / Revised: 20 June 2022 / Accepted: 22 June 2022 / Published: 24 June 2022
(This article belongs to the Special Issue Pharmaco-Toxicological Effects of Novel Psychoactive Substances 2.0)
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-[18F]-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. View Full-Text
Keywords: 4-[18F]-ADAM; MDMA; SERT; amitriptyline 4-[18F]-ADAM; MDMA; SERT; amitriptyline
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MDPI and ACS Style

Tsai, C.-J.; Chiu, C.-H.; Kuo, Y.-Y.; Huang, W.-S.; Yu, T.-H.; Flores, L.G., II; Yeh, S.H.-H.; Ma, K.-H. Amitriptyline Accelerates SERT Binding Recovery in a Rat 3,4-Methylenedioxymethamphetamine (MDMA) Model: In Vivo 4-[18F]-ADAM PET Imaging. Int. J. Mol. Sci. 2022, 23, 7035. https://doi.org/10.3390/ijms23137035

AMA Style

Tsai C-J, Chiu C-H, Kuo Y-Y, Huang W-S, Yu T-H, Flores LG II, Yeh SH-H, Ma K-H. Amitriptyline Accelerates SERT Binding Recovery in a Rat 3,4-Methylenedioxymethamphetamine (MDMA) Model: In Vivo 4-[18F]-ADAM PET Imaging. International Journal of Molecular Sciences. 2022; 23(13):7035. https://doi.org/10.3390/ijms23137035

Chicago/Turabian Style

Tsai, Chi-Jung, Chuang-Hsin Chiu, Yu-Yeh Kuo, Wen-Sheng Huang, Tsung-Hsun Yu, Leo Garcia Flores II, Skye Hsin-Hsien Yeh, and Kuo-Hsing Ma. 2022. "Amitriptyline Accelerates SERT Binding Recovery in a Rat 3,4-Methylenedioxymethamphetamine (MDMA) Model: In Vivo 4-[18F]-ADAM PET Imaging" International Journal of Molecular Sciences 23, no. 13: 7035. https://doi.org/10.3390/ijms23137035

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