PMID- 35806049
OWN - NLM
STAT- MEDLINE
DCOM- 20220712
LR  - 20220716
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 13
DP  - 2022 Jun 24
TI  - Amitriptyline Accelerates SERT Binding Recovery in a Rat 
      3,4-Methylenedioxymethamphetamine (MDMA) Model: In Vivo 4-[(18)F]-ADAM PET 
      Imaging.
LID - 10.3390/ijms23137035 [doi]
LID - 7035
AB  - 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-[(18)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.
FAU - Tsai, Chi-Jung
AU  - Tsai CJ
AD  - Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei 110, 
      Taiwan.
FAU - Chiu, Chuang-Hsin
AU  - Chiu CH
AUID- ORCID: 0000-0002-7275-6558
AD  - Department of Nuclear Medicine, Tri-Service General Hospital, Taipei 114, Taiwan.
FAU - Kuo, Yu-Yeh
AU  - Kuo YY
AD  - Department of Nursing, Hsin-Sheng College of Medical Care and Management, Taoyuan 
      325, Taiwan.
FAU - Huang, Wen-Sheng
AU  - Huang WS
AD  - Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei 110, 
      Taiwan.
AD  - Department of Nuclear Medicine, Cheng-Hsin General Hospital, Taipei 112, Taiwan.
FAU - Yu, Tsung-Hsun
AU  - Yu TH
AD  - Brain Research Center, National Yang Ming Chaio Tung University, Taipei 112, 
      Taiwan.
FAU - Flores, Leo Garcia 2nd
AU  - Flores LG 2nd
AD  - Radiomedix, Inc., Houston, TX 77042, USA.
FAU - Yeh, Skye Hsin-Hsien
AU  - Yeh SH
AUID- ORCID: 0000-0002-7495-1146
AD  - Brain Research Center, National Yang Ming Chaio Tung University, Taipei 112, 
      Taiwan.
AD  - School of Medicine, National Defense Medical Center, Taipei 110, Taiwan.
FAU - Ma, Kuo-Hsing
AU  - Ma KH
AD  - Department of Biology and Anatomy, National Defense Medi Center, Taipei 110, 
      Taiwan.
LA  - eng
GR  - MOST-109-2314-B-038-151, MOST-110-2314-B-A49A-528, 
      109-2314-B-016-014-MY2/Ministry of Science and Technology R.O.C./
GR  - 110M0156/Development Center for Biotechnology/
PT  - Journal Article
DEP - 20220624
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Fluorine Radioisotopes)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 1806D8D52K (Amitriptyline)
RN  - GZ5I74KB8G (Fluorine-18)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Amitriptyline/metabolism
MH  - Animals
MH  - Brain/metabolism
MH  - Fluorine Radioisotopes
MH  - *N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - *Neuroprotective Agents/pharmacology
MH  - Positron-Emission Tomography/methods
MH  - Rats
MH  - Serotonin Plasma Membrane Transport Proteins/metabolism
PMC - PMC9266335
OTO - NOTNLM
OT  - 4-[18F]-ADAM
OT  - MDMA
OT  - SERT
OT  - amitriptyline
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/10 06:00
MHDA- 2022/07/14 06:00
PMCR- 2022/06/24
CRDT- 2022/07/09 01:11
PHST- 2022/06/01 00:00 [received]
PHST- 2022/06/20 00:00 [revised]
PHST- 2022/06/22 00:00 [accepted]
PHST- 2022/07/09 01:11 [entrez]
PHST- 2022/07/10 06:00 [pubmed]
PHST- 2022/07/14 06:00 [medline]
PHST- 2022/06/24 00:00 [pmc-release]
AID - ijms23137035 [pii]
AID - ijms-23-07035 [pii]
AID - 10.3390/ijms23137035 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Jun 24;23(13):7035. doi: 10.3390/ijms23137035.