Amitriptyline Accelerates SERT Binding Recovery in a Rat 3,4-Methylenedioxymethamphetamine (MDMA) Model: In Vivo 4-[18F]-ADAM PET Imaging
Chi-Jung Tsai, Chuang-Hsin Chiu, Yu-Yeh Kuo, Wen-Sheng Huang, Tsung-Hsun Yu, Leo Garcia Flores, Skye Hsin-Hsien Yeh, Kuo-Hsing Ma
International Journal of Molecular Sciences June 24, 2022 DOI: 10.3390/ijms23137035 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Longitudinal Peer reviewed |
|---|---|
| Population | Rats treated with MDMA |
| Interventions | MDMA Amitriptyline |
| Duration | 35 days |
| Measures | 4-[18F]-ADAM PET imaging, immunochemical staining |
| Topics | MDMA |
| Key points | MDMA reduced SERT binding in rat brains, with region-specific recovery from about 71% of baseline at day 14 to about 91% at day 35 of abstinence. Amitriptyline increased SERT binding in all brain regions, improving recovery by roughly 18% at day 14, and increased serotonergic fiber density in the cingulate and thalamus, suggesting possible neuroprotective effects. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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