PMID- 30826457
OWN - NLM
STAT- MEDLINE
DCOM- 20200213
LR  - 20200213
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 142
DP  - 2019 Apr
TI  - Autophagy inhibition plays a protective role against 3, 
      4-methylenedioxymethamphetamine (MDMA)-induced loss of serotonin transporters and 
      depressive-like behaviors in rats.
PG  - 283-293
LID - S1043-6618(18)31305-7 [pii]
LID - 10.1016/j.phrs.2019.02.026 [doi]
AB  - The 3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug, 
      which ultimately leads to serotonergic (5-HT) neurotoxicity and psychiatric 
      disorders. Previous in vitro studies have consistently demonstrated that MDMA 
      provokes autophagic activation, as well as damage of 5-HT axons and nerve fibers. 
      So far, whether autophagy, a well-conserved cellular process that is critical for 
      cell fate, also participates in MDMA-induced neurotoxicity in vivo remains 
      elusive. Here, we first examined time-course of autophagy-related changes during 
      repeated administration of MDMA (10 mg/kg s.c. twice daily for 4 consecutive 
      days) using immunofluorescent staining for tryptophan hydroxylase and 
      microtubule-associated protein 1 light chain 3 beta in rats. We also evaluated 
      the protective effects of 3-methyadanine (3-MA, an autophagy inhibitor, 15 mg/kg 
      i.p.) against MDMA-induced acute and long-term reductions in serotonin 
      transporters (SERT) density in various brain regions using immunohistochemical 
      staining and positron emission tomography (PET) imaging respectively. Plasma 
      corticosterone measurements and forced swim tests were performed to evaluate the 
      depressive performance. The staining results showed that repeated administration 
      of MDMA increased expression of autophagosome and caused reduction in SERT 
      densities of striatum and frontal cortex, which was ameliorated in the presence 
      of 3-MA. PET imaging data also revealed that 3-MA could ameliorate MDMA-induced 
      long-term decreased SERT availability in various brain regions of rats. 
      Furthermore, immobility time of forced swim tests and plasma corticosterone 
      levels were less in the group of MDMA co-injected with 3-MA compared with that of 
      MDMA group. Together, these findings suggest that autophagy inhibition may confer 
      protection against neurobiological and behavioral changes induced by MDMA.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Shih, Jui-Hu
AU  - Shih JH
AD  - Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan; 
      School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
FAU - Chiu, Chuang-Hsin
AU  - Chiu CH
AD  - Department of Nuclear Medicine, Tri-Service General Hospital, National Defense 
      Medical Center, Taipei, Taiwan.
FAU - Ma, Kuo-Hsing
AU  - Ma KH
AD  - Department of Biology and Anatomy, National Defense Medical Center, Taipei, 
      Taiwan.
FAU - Huang, Yuahn-Sieh
AU  - Huang YS
AD  - Department of Biology and Anatomy, National Defense Medical Center, Taipei, 
      Taiwan.
FAU - Shiue, Chyng-Yann
AU  - Shiue CY
AD  - Department of Nuclear Medicine, Tri-Service General Hospital, National Defense 
      Medical Center, Taipei, Taiwan.
FAU - Yeh, Ting-Yin
AU  - Yeh TY
AD  - Department of Biology and Anatomy, National Defense Medical Center, Taipei, 
      Taiwan.
FAU - Kao, Li-Ting
AU  - Kao LT
AD  - Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan; 
      Graduate Institute of Life Science, National Defense Medical Center, Taipei, 
      Taiwan.
FAU - Lin, Yang-Yi
AU  - Lin YY
AD  - Department of Pharmacy, Chi Mei Medical Center, Tainan, Taiwan.
FAU - Li, I-Hsun
AU  - Li IH
AD  - Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan; 
      School of Pharmacy, National Defense Medical Center, Taipei, Taiwan. Electronic 
      address: lhs01077@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190228
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 5142-23-4 (3-methyladenine)
RN  - JAC85A2161 (Adenine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Animals
MH  - *Autophagy
MH  - Behavior, Animal/drug effects
MH  - Brain/drug effects/*metabolism
MH  - Depression/drug therapy/*metabolism
MH  - Male
MH  - *N-Methyl-3,4-methylenedioxyamphetamine
MH  - Neuroprotective Agents/pharmacology
MH  - Rats, Sprague-Dawley
MH  - Serotonergic Neurons/drug effects
MH  - Serotonin Plasma Membrane Transport Proteins/*metabolism
OTO - NOTNLM
OT  - 3-methyladenine
OT  - Autophagy
OT  - Depression
OT  - MDMA
OT  - Neurotoxicity
OT  - Serotonin transporter
EDAT- 2019/03/04 06:00
MHDA- 2020/02/14 06:00
CRDT- 2019/03/04 06:00
PHST- 2018/09/01 00:00 [received]
PHST- 2018/12/27 00:00 [revised]
PHST- 2019/02/24 00:00 [accepted]
PHST- 2019/03/04 06:00 [pubmed]
PHST- 2020/02/14 06:00 [medline]
PHST- 2019/03/04 06:00 [entrez]
AID - S1043-6618(18)31305-7 [pii]
AID - 10.1016/j.phrs.2019.02.026 [doi]
PST - ppublish
SO  - Pharmacol Res. 2019 Apr;142:283-293. doi: 10.1016/j.phrs.2019.02.026. Epub 2019 
      Feb 28.