PMID- 24760865
OWN - NLM
STAT- MEDLINE
DCOM- 20140609
LR  - 20211021
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 34
IP  - 17
DP  - 2014 Apr 23
TI  - Infralimbic BDNF/TrkB enhancement of GluN2B currents facilitates extinction of a 
      cocaine-conditioned place preference.
PG  - 6057-64
LID - 10.1523/JNEUROSCI.4980-13.2014 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) regulates synaptic activity and 
      behavioral flexibility, and reduction of BDNF strongly predicts psychiatric 
      disorders and cognitive dysfunction. Restoration of BDNF-dependent activity could 
      alleviate these impairments, but BDNF has limited clinical utility due to its 
      pharmacokinetics. Here we demonstrate that activation of a primary BDNF target, 
      the tropomyosin-related kinase B (TrkB) receptor, enhances the amplitude and 
      prolongs the decay kinetics of N-methyl-d-aspartate receptor (NMDAR) currents in 
      male rat infralimbic prefrontal pyramidal neurons. Moreover, these effects were 
      prevented and reversed by blockade of NMDARs containing the GluN2B subunit. Our 
      results show that this signaling cascade bidirectionally regulates extinction of 
      a cocaine-induced conditioned place preference (CPP), a task that requires 
      behavioral flexibility. Blockade of infralimbic TrkB receptors or 
      GluN2B-containing NMDARs disrupted consolidation of extinction of the CPP. In 
      contrast, extinction was strengthened by potentiation of TrkB receptor activity 
      with infralimbic infusions of BDNF or systemic injections of 7,8 dihydroxyflavone 
      (7,8DHF), the newly synthesized TrkB receptor agonist. The 7,8DHF-induced 
      enhancement of extinction was prevented by infralimbic infusions of a 
      GluN2B-specific receptor antagonist, demonstrating that TrkB receptor activation 
      enhances extinction of cocaine-CPP via GluN2B-containing NMDARs. Together, 
      infralimbic TrkB receptor activation strengthens GluN2B-containing NMDAR currents 
      to support extinction learning. TrkB receptor agonists would therefore be useful 
      as pharmacological adjuncts for extinction-based therapies for treatment of 
      psychiatric disorders associated with reduced BDNF activity.
FAU - Otis, James M
AU  - Otis JM
AD  - Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 
      53201-0413.
FAU - Fitzgerald, Michael K
AU  - Fitzgerald MK
FAU - Mueller, Devin
AU  - Mueller D
LA  - eng
GR  - R03 DA027870/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (7,8-dihydroxyflavanone)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Flavanones)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Association Learning/drug effects/physiology
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cocaine/*administration & dosage
MH  - Conditioning, Operant/*drug effects/physiology
MH  - Dopamine Uptake Inhibitors/*administration & dosage
MH  - Extinction, Psychological/*drug effects/physiology
MH  - Fear/drug effects/physiology
MH  - Flavanones/pharmacology
MH  - Male
MH  - Neurons/drug effects/physiology
MH  - Rats
MH  - Receptor, trkB/*agonists
MH  - Receptors, N-Methyl-D-Aspartate/*physiology
MH  - Self Administration
PMC - PMC3996223
OTO - NOTNLM
OT  - NR2B-containing NMDA receptor
OT  - TrkB receptor
OT  - brain-derived neurotrophic factor
OT  - extinction learning
OT  - medial prefrontal cortex
OT  - patch-clamp electrophysiology
EDAT- 2014/04/25 06:00
MHDA- 2014/06/10 06:00
PMCR- 2014/10/23
CRDT- 2014/04/25 06:00
PHST- 2014/04/25 06:00 [entrez]
PHST- 2014/04/25 06:00 [pubmed]
PHST- 2014/06/10 06:00 [medline]
PHST- 2014/10/23 00:00 [pmc-release]
AID - 34/17/6057 [pii]
AID - 4980-13 [pii]
AID - 10.1523/JNEUROSCI.4980-13.2014 [doi]
PST - ppublish
SO  - J Neurosci. 2014 Apr 23;34(17):6057-64. doi: 10.1523/JNEUROSCI.4980-13.2014.