PMID- 31267156
OWN - NLM
STAT- MEDLINE
DCOM- 20200225
LR  - 20200309
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 236
IP  - 12
DP  - 2019 Dec
TI  - NMDA receptor antagonists traxoprodil and lanicemine improve 
      hippocampal-prefrontal coupling and reward-related networks in rats.
PG  - 3451-3463
LID - 10.1007/s00213-019-05310-3 [doi]
AB  - RATIONALE: The N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is known 
      to have not only a rapid antidepressant effect but also dissociative side 
      effects. Traxoprodil and lanicemine, also NMDA antagonists, are candidate 
      antidepressant drugs with fewer side effects. OBJECTIVES: In order to understand 
      their mechanism of action, we investigated the acute effects of traxoprodil and 
      lanicemine on brain connectivity using resting-state functional magnetic 
      resonance imaging (rs-fMRI). METHODS: Functional connectivity (FC) alterations 
      were examined using interregional correlation networks. Graph theoretical methods 
      were used for whole brain network analysis. As interest in NMDAR antagonists as 
      potential antidepressants was triggered by the antidepressant effect of ketamine, 
      results were compared to previous findings from our ketamine studies. RESULTS: 
      Similar to ketamine but to a smaller extent, traxoprodil increased 
      hippocampal-prefrontal (Hc-PFC) coupling. Unlike ketamine, traxoprodil decreased 
      connectivity within the PFC. Lanicemine had no effect on these properties. The 
      improvement of Hc-PFC coupling corresponds well to clinical result, showing 
      ketamine to have a greater antidepressant effect than traxoprodil, while 
      lanicemine has a weak and transient effect. Connectivity changes overlapping 
      between the drugs as well as alterations of local network properties occurred 
      mostly in reward-related regions. CONCLUSION: The antidepressant effect of NMDA 
      antagonists appears to be associated with enhanced Hc-PFC coupling. The effects 
      on local network properties and regional connectivity suggest that improvement of 
      reward processing might also be important for understanding the mechanisms 
      underlying the antidepressant effects of these drugs.
FAU - Becker, Robert
AU  - Becker R
AUID- ORCID: 0000-0003-4080-4452
AD  - Research Group Translational Imaging, Department of Neuroimaging, Central 
      Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 
      68159, Mannheim, Germany. robert.becker@zi-mannheim.de.
FAU - Gass, Natalia
AU  - Gass N
AD  - Research Group Translational Imaging, Department of Neuroimaging, Central 
      Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 
      68159, Mannheim, Germany.
FAU - Kussmaul, Lothar
AU  - Kussmaul L
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
FAU - Schmid, Bernhard
AU  - Schmid B
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
FAU - Scheuerer, Stefan
AU  - Scheuerer S
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
FAU - Schnell, David
AU  - Schnell D
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
FAU - Dorner-Ciossek, Cornelia
AU  - Dorner-Ciossek C
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
FAU - Weber-Fahr, Wolfgang
AU  - Weber-Fahr W
AD  - Research Group Translational Imaging, Department of Neuroimaging, Central 
      Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 
      68159, Mannheim, Germany.
FAU - Sartorius, Alexander
AU  - Sartorius A
AD  - Research Group Translational Imaging, Department of Neuroimaging, Central 
      Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 
      68159, Mannheim, Germany.
AD  - Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, 
      Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
LA  - eng
GR  - GA 2109/2-1/Deutsche Forschungsgemeinschaft/
GR  - SA 1869/11-2/Deutsche Forschungsgemeinschaft/
GR  - SA 1869/14-1/Deutsche Forschungsgemeinschaft/
PT  - Journal Article
DEP - 20190702
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (AZD6765)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Phenethylamines)
RN  - 0 (Piperidines)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - BD2A56I30W (traxoprodil mesylate)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Hippocampus/diagnostic imaging/*drug effects/physiology
MH  - Magnetic Resonance Imaging/methods
MH  - Male
MH  - Phenethylamines/*pharmacology
MH  - Piperidines/*pharmacology
MH  - Prefrontal Cortex/diagnostic imaging/*drug effects/physiology
MH  - Pyridines/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/physiology
MH  - *Reward
OTO - NOTNLM
OT  - Hippocampal-prefrontal coupling
OT  - NMDA antagonists
OT  - Networks
OT  - fMRI
EDAT- 2019/07/04 06:00
MHDA- 2020/02/26 06:00
CRDT- 2019/07/04 06:00
PHST- 2019/04/03 00:00 [received]
PHST- 2019/06/18 00:00 [accepted]
PHST- 2019/07/04 06:00 [pubmed]
PHST- 2020/02/26 06:00 [medline]
PHST- 2019/07/04 06:00 [entrez]
AID - 10.1007/s00213-019-05310-3 [pii]
AID - 10.1007/s00213-019-05310-3 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2019 Dec;236(12):3451-3463. doi: 
      10.1007/s00213-019-05310-3. Epub 2019 Jul 2.