PMID- 31809766
OWN - NLM
STAT- MEDLINE
DCOM- 20210503
LR  - 20210503
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Print)
IS  - 0166-4328 (Linking)
VI  - 380
DP  - 2020 Feb 17
TI  - The acute toxic and neurotoxic effects of 3,4-methylenedioxymethamphetamine are 
      more pronounced in adolescent than adult mice.
PG  - 112413
LID - S0166-4328(19)31187-8 [pii]
LID - 10.1016/j.bbr.2019.112413 [doi]
AB  - 3,4-methylenedioxymethamphetamine (MDMA) recently achieved breakthrough status 
      from the Food and Drug Administration (FDA) for post-traumatic stress disorder 
      (PTSD). However, evidence indicates that exposure to toxic doses of MDMA can lead 
      to long-lasting dysregulation of brain monoaminergic neurotransmitters, primarily 
      from studies conducted in young adult rodents. To date, there is a paucity of 
      data on whether toxic doses of MDMA can differentially affect neurotransmitter 
      systems in adolescents and mature adults, which is an important question as 
      adolescents and adults may be differentially vulnerable to MDMA abuse. In the 
      current study, adolescent (6-7 weeks of age) and mature adult (16-18 weeks of 
      age) male, Swiss-Webster mice were exposed to MDMA (20 mg/kg) using a binge-like 
      dosing regimen (4 administrations spaced every 2 h). Acute lethality, acute 
      hyperthermia, and acute decreases in body weight following MDMA administration 
      were more pronounced in adolescent than adult mice. Likewise, acute loss of 
      striatal dopamine neurochemistry was also exacerbated in adolescents, as 
      determined by high-pressure liquid chromatography coupled to electrochemical 
      detection. Exposure to MDMA induced greater turnover of dopamine into its major 
      metabolite dihydroxyphenylacetic acid (DOPAC) in adolescents, but not in adults, 
      suggesting a novel mechanism through which adolescents may show increased 
      vulnerability to the acute toxic and neurotoxic effects of MDMA, or conversely 
      that mature adults show greater protection. These data caution that MDMA exposure 
      in adolescence may be particularly dangerous and that the therapeutic window for 
      MDMA may differ between adolescents and mature adults.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Chitre, Neha Milind
AU  - Chitre NM
AD  - Department of Pharmaceutical Sciences, Mercer University College of Pharmacy, 
      Mercer University Health Sciences Center, Atlanta, GA, USA.
FAU - Bagwell, Monique Simone
AU  - Bagwell MS
AD  - Department of Pharmaceutical Sciences, Mercer University College of Pharmacy, 
      Mercer University Health Sciences Center, Atlanta, GA, USA.
FAU - Murnane, Kevin Sean
AU  - Murnane KS
AD  - Department of Pharmaceutical Sciences, Mercer University College of Pharmacy, 
      Mercer University Health Sciences Center, Atlanta, GA, USA. Electronic address: 
      murnane_ks@mercer.edu.
LA  - eng
GR  - R21 DA040907/DA/NIDA NIH HHS/United States
GR  - R21 NS100512/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191203
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Central Nervous System Stimulants)
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Dihydroxyphenylacetic Acid/*metabolism
MH  - Age Factors
MH  - Animals
MH  - Body Weight/*drug effects
MH  - Central Nervous System Stimulants/administration & dosage/*toxicity
MH  - Corpus Striatum/*drug effects/metabolism
MH  - Dopamine/*metabolism
MH  - Hyperthermia/*chemically induced
MH  - Male
MH  - Mice
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*toxicity
MH  - Prefrontal Cortex/*drug effects/metabolism
PMC - PMC6984008
MID - NIHMS1546460
OTO - NOTNLM
OT  - Adolescence
OT  - Dopamine
OT  - Dopamine turnover
OT  - Lethality
OT  - MDMA
OT  - Neurotoxicity
COIS- COI: The authors have no conflicts of interest to disclose.
EDAT- 2019/12/07 06:00
MHDA- 2021/05/04 06:00
PMCR- 2021/02/17
CRDT- 2019/12/07 06:00
PHST- 2019/07/31 00:00 [received]
PHST- 2019/12/02 00:00 [revised]
PHST- 2019/12/02 00:00 [accepted]
PHST- 2019/12/07 06:00 [pubmed]
PHST- 2021/05/04 06:00 [medline]
PHST- 2019/12/07 06:00 [entrez]
PHST- 2021/02/17 00:00 [pmc-release]
AID - S0166-4328(19)31187-8 [pii]
AID - 10.1016/j.bbr.2019.112413 [doi]
PST - ppublish
SO  - Behav Brain Res. 2020 Feb 17;380:112413. doi: 10.1016/j.bbr.2019.112413. Epub 
      2019 Dec 3.