PMID- 37235749
OWN - NLM
STAT- MEDLINE
DCOM- 20230626
LR  - 20240320
IS  - 1469-5111 (Electronic)
IS  - 1461-1457 (Print)
IS  - 1461-1457 (Linking)
VI  - 26
IP  - 6
DP  - 2023 Jun 23
TI  - Chronic 3,4-Methylenedioxymethamphetamine (MDMA) Use Is Related to Glutamate and 
      GABA Concentrations in the Striatum But Not the Anterior Cingulate Cortex.
PG  - 438-450
LID - 10.1093/ijnp/pyad023 [doi]
AB  - BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely used 
      recreational substance inducing acute release of serotonin. Previous studies in 
      chronic MDMA users demonstrated selective adaptations in the serotonin system, 
      which were assumed to be associated with cognitive deficits. However, serotonin 
      functions are strongly entangled with glutamate as well as gamma-aminobutyric acid 
      (GABA) neurotransmission, and studies in MDMA-exposed rats show long-term 
      adaptations in glutamatergic and GABAergic signaling. METHODS: We used proton 
      magnetic resonance spectroscopy (MRS) to measure the glutamate-glutamine complex 
      (GLX) and GABA concentrations in the left striatum and medial anterior cingulate 
      cortex (ACC) of 44 chronic but recently abstinent MDMA users and 42 MDMA-naive 
      healthy controls. While the Mescher-Garwood point-resolved-spectroscopy sequence 
      (MEGA-PRESS) is best suited to quantify GABA, recent studies reported poor 
      agreement between conventional short-echo-time PRESS and MEGA-PRESS for GLX 
      measures. Here, we applied both sequences to assess their agreement and potential 
      confounders underlying the diverging results. RESULTS: Chronic MDMA users showed 
      elevated GLX levels in the striatum but not the ACC. Regarding GABA, we found no 
      group difference in either region, although a negative association with MDMA use 
      frequency was observed in the striatum. Overall, GLX measures from MEGA-PRESS, 
      with its longer echo time, appeared to be less confounded by macromolecule signal 
      than the short-echo-time PRESS and thus provided more robust results. CONCLUSION: 
      Our findings suggest that MDMA use affects not only serotonin but also striatal 
      GLX and GABA concentrations. These insights may offer new mechanistic 
      explanations for cognitive deficits (e.g., impaired impulse control) observed in 
      MDMA users.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of CINP.
FAU - Zimmermann, Josua
AU  - Zimmermann J
AD  - Experimental and Clinical Pharmacopsychology, Department of Psychiatry, 
      Psychotherapy, and Psychosomatics, Psychiatric University Hospital Zurich, 
      University of Zurich, Zurich, Switzerland.
AD  - Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
AD  - Neuroscience Center Zurich, ETH Zurich and University of Zurich, Zurich, 
      Switzerland.
FAU - Zolch, Niklaus
AU  - Zolch N
AD  - Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric 
      University Hospital Zurich, University of Zurich, Zurich, Switzerland.
AD  - Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.
FAU - Coray, Rebecca
AU  - Coray R
AD  - Experimental and Clinical Pharmacopsychology, Department of Psychiatry, 
      Psychotherapy, and Psychosomatics, Psychiatric University Hospital Zurich, 
      University of Zurich, Zurich, Switzerland.
AD  - Neuroscience Center Zurich, ETH Zurich and University of Zurich, Zurich, 
      Switzerland.
FAU - Bavato, Francesco
AU  - Bavato F
AD  - Experimental and Clinical Pharmacopsychology, Department of Psychiatry, 
      Psychotherapy, and Psychosomatics, Psychiatric University Hospital Zurich, 
      University of Zurich, Zurich, Switzerland.
FAU - Friedli, Nicole
AU  - Friedli N
AD  - Experimental and Clinical Pharmacopsychology, Department of Psychiatry, 
      Psychotherapy, and Psychosomatics, Psychiatric University Hospital Zurich, 
      University of Zurich, Zurich, Switzerland.
FAU - Baumgartner, Markus R
AU  - Baumgartner MR
AD  - Center for Forensic Hair Analytics, Institute of Forensic Medicine, University of 
      Zurich, Zurich, Switzerland.
FAU - Steuer, Andrea E
AU  - Steuer AE
AD  - Department of Forensic Pharmacology and Toxicology, Institute of Forensic 
      Medicine, University of Zurich, Zurich, Switzerland.
FAU - Opitz, Antje
AU  - Opitz A
AD  - Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, TU 
      Dresden, Dresden, Germany.
FAU - Werner, Annett
AU  - Werner A
AD  - Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, TU 
      Dresden, Dresden, Germany.
FAU - Oeltzschner, Georg
AU  - Oeltzschner G
AD  - Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins 
      University School of Medicine, Baltimore, Maryland, USA.
AD  - F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger 
      Institute, Baltimore, Maryland, USA.
FAU - Seifritz, Erich
AU  - Seifritz E
AD  - Neuroscience Center Zurich, ETH Zurich and University of Zurich, Zurich, 
      Switzerland.
AD  - Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric 
      University Hospital Zurich (Drs Zolch and Seifritz), University of Zurich, 
      Zurich, Switzerland.
FAU - Stock, Ann-Kathrin
AU  - Stock AK
AD  - Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, TU 
      Dresden, Dresden, Germany.
AD  - Biopsychology, Faculty of Psychology, School of Science, TU Dresden, Germany.
FAU - Beste, Christian
AU  - Beste C
AD  - Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, TU 
      Dresden, Dresden, Germany.
FAU - Cole, David M
AU  - Cole DM
AD  - Experimental and Clinical Pharmacopsychology, Department of Psychiatry, 
      Psychotherapy, and Psychosomatics, Psychiatric University Hospital Zurich, 
      University of Zurich, Zurich, Switzerland.
AD  - Neuroscience Center Zurich, ETH Zurich and University of Zurich, Zurich, 
      Switzerland.
FAU - Quednow, Boris B
AU  - Quednow BB
AUID- ORCID: 0000-0001-7933-2865
AD  - Experimental and Clinical Pharmacopsychology, Department of Psychiatry, 
      Psychotherapy, and Psychosomatics, Psychiatric University Hospital Zurich, 
      University of Zurich, Zurich, Switzerland.
AD  - Neuroscience Center Zurich, ETH Zurich and University of Zurich, Zurich, 
      Switzerland.
LA  - eng
GR  - P50 HD103538/HD/NICHD NIH HHS/United States
GR  - 320030L_179450/SNSF_/Swiss National Science Foundation/Switzerland
PT  - Journal Article
PL  - England
TA  - Int J Neuropsychopharmacol
JT  - The international journal of neuropsychopharmacology
JID - 9815893
RN  - 3KX376GY7L (Glutamic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - 333DO1RDJY (Serotonin)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 0RH81L854J (Glutamine)
SB  - IM
CIN - Int J Neuropsychopharmacol. 2023 Sep 25;26(9):616-617. PMID: 37549963
MH  - Rats
MH  - Animals
MH  - *Glutamic Acid
MH  - *N-Methyl-3,4-methylenedioxyamphetamine
MH  - Magnetic Resonance Spectroscopy/methods
MH  - Serotonin
MH  - Gyrus Cinguli/diagnostic imaging
MH  - gamma-Aminobutyric Acid
MH  - Glutamine
PMC - PMC10289146
OTO - NOTNLM
OT  - GABA
OT  - MDMA
OT  - MEGA-PRESS
OT  - MRS
OT  - PRESS
OT  - glutamate
OT  - serotonin
EDAT- 2023/05/26 19:14
MHDA- 2023/06/26 06:42
PMCR- 2023/05/26
CRDT- 2023/05/26 14:53
PHST- 2023/01/09 00:00 [received]
PHST- 2023/05/24 00:00 [accepted]
PHST- 2023/06/26 06:42 [medline]
PHST- 2023/05/26 19:14 [pubmed]
PHST- 2023/05/26 14:53 [entrez]
PHST- 2023/05/26 00:00 [pmc-release]
AID - 7180809 [pii]
AID - pyad023 [pii]
AID - 10.1093/ijnp/pyad023 [doi]
PST - ppublish
SO  - Int J Neuropsychopharmacol. 2023 Jun 23;26(6):438-450. doi: 10.1093/ijnp/pyad023.