PMID- 22084102
OWN - NLM
STAT- MEDLINE
DCOM- 20120123
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 108
IP  - 48
DP  - 2011 Nov 29
TI  - Heroin relapse requires long-term potentiation-like plasticity mediated by 
      NMDA2b-containing receptors.
PG  - 19407-12
LID - 10.1073/pnas.1112052108 [doi]
AB  - Persistent relapse to addictive drugs constitutes the most challenging problem in 
      addiction therapy, and is linked to impaired prefrontal cortex regulation of 
      motivated behaviors involving the nucleus accumbens. Using a rat model of heroin 
      addiction, we show that relapse requires long-term potentiation (LTP)-like 
      increases in synaptic strength in the prefrontal cortex projection to the nucleus 
      accumbens. The increased synaptic strength was paralleled by dendritic spine 
      enlargement in accumbens spiny neurons and required up-regulated surface 
      expression of NMDA2b-containing receptors (NR2B). Accordingly, blocking NR2B 
      before reinstating heroin-seeking prevented the induction of LTP-like changes in 
      spine remodeling and synaptic strength, and inhibited heroin relapse. These data 
      show that LTP-like neuroplasticity in prefrontal-accumbens synapses is initiated 
      by NR2B stimulation and strongly contributes to heroin relapse. Moreover, the 
      data reveal NR2B-containing NMDA receptors as a previously unexplored therapeutic 
      target for treating heroin addiction.
FAU - Shen, Haowei
AU  - Shen H
AD  - Department of Neurosciences, Medical University of South Carolina, Charleston, SC 
      29425, USA. shenhw@musc.edu
FAU - Moussawi, Khaled
AU  - Moussawi K
FAU - Zhou, Wenhua
AU  - Zhou W
FAU - Toda, Shigenobu
AU  - Toda S
FAU - Kalivas, Peter W
AU  - Kalivas PW
LA  - eng
GR  - P50 DA015369/DA/NIDA NIH HHS/United States
GR  - R01 DA003906/DA/NIDA NIH HHS/United States
GR  - R37 DA003906/DA/NIDA NIH HHS/United States
GR  - DA015369/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111114
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - R8OE3P6O5S (ifenprodil)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Biotinylation
MH  - Dendrites/ultrastructure
MH  - Electrophysiology
MH  - Extinction, Psychological/physiology
MH  - Heroin Dependence/*physiopathology
MH  - Long-Term Potentiation/*physiology
MH  - Microscopy, Confocal
MH  - Piperidines
MH  - Prefrontal Cortex/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Recurrence
MH  - Self Administration
MH  - Synaptic Transmission/*physiology
PMC - PMC3228456
COIS- The authors declare no conflict of interest.
EDAT- 2011/11/16 06:00
MHDA- 2012/01/24 06:00
PMCR- 2012/05/29
CRDT- 2011/11/16 06:00
PHST- 2011/11/16 06:00 [entrez]
PHST- 2011/11/16 06:00 [pubmed]
PHST- 2012/01/24 06:00 [medline]
PHST- 2012/05/29 00:00 [pmc-release]
AID - 1112052108 [pii]
AID - 201112052 [pii]
AID - 10.1073/pnas.1112052108 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19407-12. doi: 
      10.1073/pnas.1112052108. Epub 2011 Nov 14.