PMID- 36175138
OWN - NLM
STAT- MEDLINE
DCOM- 20230306
LR  - 20230310
IS  - 1535-5667 (Electronic)
IS  - 0161-5505 (Linking)
VI  - 64
IP  - 3
DP  - 2023 Mar
TI  - Neurovascular Uncoupling: Multimodal Imaging Delineates the Acute Effects of 
      3,4-Methylenedioxymethamphetamine.
PG  - 466-471
LID - 10.2967/jnumed.122.264391 [doi]
AB  - Psychedelic compounds such as 3,4-methylenedioxymethamphetamine (MDMA) have 
      attracted increasing interest in recent years because of their therapeutic 
      potential in psychiatric disorders. To understand the acute effects of 
      psychedelic drugs in vivo, blood-oxygenation-level-dependent (BOLD) functional 
      MRI (fMRI) has been widely used. In particular, fMRI studies have suggested that 
      MDMA leads to inhibition of brain activity, challenging previous hypotheses 
      indicating mainly excitatory effects based, among others, on increased metabolism 
      shown by (18)F-FDG functional PET (fPET). However, interpretation of hemodynamic 
      changes induced by psychedelics is difficult because of their potent vascular 
      effects. Methods: We aimed to delineate the acute effects of MDMA using 
      simultaneous PET/fMRI in rats. For this purpose, hemodynamic changes measured by 
      BOLD fMRI were related to alterations in glucose utilization and serotonin 
      transporter (SERT) occupancy using (18)F-FDG fPET/fMRI and (11)C-DASB PET/fMRI. 
      Results: We show that MDMA induces localized increases in glucose metabolism in 
      limbic projection areas involved in emotional processing. The increased glucose 
      metabolism was accompanied by global cerebral and extracerebral hemodynamic 
      decreases. We further demonstrated a strong correlation between SERT occupancies 
      and regional BOLD reductions after acute MDMA administration. Conclusion: Our 
      data indicate that hemodynamic decreases after acute MDMA administration are of a 
      nonneuronal nature and initiate peripherally. Within the brain, MDMA triggers 
      neuronal activation in limbic projection areas, whereas increased serotonin 
      levels induced by SERT blockage cause neurovascular uncoupling through direct 
      vascular effects. Correct understanding of the in vivo mechanism of MDMA not only 
      supports ongoing research but also warrants a reassessment of previous studies on 
      neuronal effects of psychedelics relying on neurovascular coupling and recommends 
      (18)F-FDG fPET as a potentially more robust measure for pharmacologic research.
CI  - (c) 2023 by the Society of Nuclear Medicine and Molecular Imaging.
FAU - Ionescu, Tudor M
AU  - Ionescu TM
AD  - Werner Siemens Imaging Center, Department of Preclinical Imaging and 
      Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.
FAU - Amend, Mario
AU  - Amend M
AD  - Werner Siemens Imaging Center, Department of Preclinical Imaging and 
      Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.
FAU - Watabe, Tadashi
AU  - Watabe T
AD  - Werner Siemens Imaging Center, Department of Preclinical Imaging and 
      Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.
AD  - Department of Nuclear Medicine and Tracer Kinetics, Osaka University, Osaka, 
      Japan; and.
FAU - Hatazawa, Jun
AU  - Hatazawa J
AD  - Department of Nuclear Medicine and Tracer Kinetics, Osaka University, Osaka, 
      Japan; and.
FAU - Maurer, Andreas
AU  - Maurer A
AD  - Werner Siemens Imaging Center, Department of Preclinical Imaging and 
      Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.
FAU - Reischl, Gerald
AU  - Reischl G
AD  - Werner Siemens Imaging Center, Department of Preclinical Imaging and 
      Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.
AD  - Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed 
      Tumor Therapies", University of Tuebingen, Tuebingen, Germany.
FAU - Pichler, Bernd J
AU  - Pichler BJ
AD  - Werner Siemens Imaging Center, Department of Preclinical Imaging and 
      Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.
AD  - Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed 
      Tumor Therapies", University of Tuebingen, Tuebingen, Germany.
FAU - Wehrl, Hans F
AU  - Wehrl HF
AD  - Werner Siemens Imaging Center, Department of Preclinical Imaging and 
      Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.
FAU - Herfert, Kristina
AU  - Herfert K
AD  - Werner Siemens Imaging Center, Department of Preclinical Imaging and 
      Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany; 
      kristina.herfert@med.uni-tuebingen.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220929
PL  - United States
TA  - J Nucl Med
JT  - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
JID - 0217410
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 0 (Hallucinogens)
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *N-Methyl-3,4-methylenedioxyamphetamine/pharmacology/metabolism
MH  - Fluorodeoxyglucose F18/metabolism
MH  - *Hallucinogens/pharmacology/metabolism
MH  - Brain/metabolism
MH  - Multimodal Imaging
MH  - Glucose/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/metabolism
MH  - Positron-Emission Tomography/methods
MH  - Magnetic Resonance Imaging/methods
OTO - NOTNLM
OT  - PET/fMRI
OT  - hemodynamics
OT  - metabolism
OT  - methylenedioxymethamphetamine
OT  - neurovascular coupling
OT  - serotonin
EDAT- 2022/09/30 06:00
MHDA- 2023/03/07 06:00
CRDT- 2022/09/29 21:41
PHST- 2022/05/26 00:00 [received]
PHST- 2022/09/14 00:00 [revised]
PHST- 2022/09/30 06:00 [pubmed]
PHST- 2023/03/07 06:00 [medline]
PHST- 2022/09/29 21:41 [entrez]
AID - jnumed.122.264391 [pii]
AID - 10.2967/jnumed.122.264391 [doi]
PST - ppublish
SO  - J Nucl Med. 2023 Mar;64(3):466-471. doi: 10.2967/jnumed.122.264391. Epub 2022 Sep 
      29.