PMID- 21368124
OWN - NLM
STAT- MEDLINE
DCOM- 20110526
LR  - 20220309
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 108
IP  - 10
DP  - 2011 Mar 8
TI  - Balanced NMDA receptor activity in dopamine D1 receptor (D1R)- and D2R-expressing 
      medium spiny neurons is required for amphetamine sensitization.
PG  - 4206-11
LID - 10.1073/pnas.1101424108 [doi]
AB  - Signaling through N-methyl-D-aspartate-type glutamate receptors (NMDARs) is 
      essential for the development of behavioral sensitization to psychostimulants 
      such as amphetamine (AMPH). However, the cell type and brain region in which 
      NMDAR signaling is required for AMPH sensitization remain unresolved. Here we use 
      selective inactivation of Grin1, the gene encoding the essential NR1 subunit of 
      NMDARs, in dopamine neurons or their medium spiny neuron (MSN) targets, to 
      address this issue. We show that NMDAR signaling in dopamine neurons is not 
      required for behavioral sensitization to AMPH. Conversely, removing NMDARs from 
      MSNs that express the dopamine D1 receptor (D1R) significantly attenuated AMPH 
      sensitization, and conditional, virus-mediated restoration of NR1 in D1R neurons 
      in the nucleus accumbens (NAc) of these animals rescued sensitization. 
      Interestingly, sensitization could also be restored by virus-mediated 
      inactivation of NR1 in all remaining neurons in the NAc of animals lacking NMDARs 
      on D1R neurons, or by removing NMDARs from all MSNs. Taken together, these data 
      indicate that unbalanced loss of NMDAR signaling in D1R MSNs alone prevents AMPH 
      sensitization, whereas a balanced loss of NMDARs from both D1R and dopamine D2 
      receptor-expressing (D2R) MSNs is permissive for sensitization.
FAU - Beutler, Lisa R
AU  - Beutler LR
AD  - Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
FAU - Wanat, Matthew J
AU  - Wanat MJ
FAU - Quintana, Albert
AU  - Quintana A
FAU - Sanz, Elisenda
AU  - Sanz E
FAU - Bamford, Nigel S
AU  - Bamford NS
FAU - Zweifel, Larry S
AU  - Zweifel LS
FAU - Palmiter, Richard D
AU  - Palmiter RD
LA  - eng
GR  - F32-DA026273/DA/NIDA NIH HHS/United States
GR  - NS060803/NS/NINDS NIH HHS/United States
GR  - P30 HD002274/HD/NICHD NIH HHS/United States
GR  - R01 NS060803/NS/NINDS NIH HHS/United States
GR  - NS052536/NS/NINDS NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - HD02274/HD/NICHD NIH HHS/United States
GR  - T32 GM007735/GM/NIGMS NIH HHS/United States
GR  - T32 GM07735/GM/NIGMS NIH HHS/United States
GR  - K02 NS052536/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110222
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 (Amphetamines)
RN  - 0 (Receptors, Dopamine D1)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Amphetamines/*pharmacology
MH  - Animals
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/*drug effects/metabolism
MH  - Receptors, Dopamine D1/*metabolism
MH  - Receptors, Dopamine D2/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Signal Transduction
PMC - PMC3054029
COIS- The authors declare no conflict of interest.
EDAT- 2011/03/04 06:00
MHDA- 2011/05/27 06:00
PMCR- 2011/02/22
CRDT- 2011/03/04 06:00
PHST- 2011/03/04 06:00 [entrez]
PHST- 2011/03/04 06:00 [pubmed]
PHST- 2011/05/27 06:00 [medline]
PHST- 2011/02/22 00:00 [pmc-release]
AID - 1101424108 [pii]
AID - 201101424 [pii]
AID - 10.1073/pnas.1101424108 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4206-11. doi: 
      10.1073/pnas.1101424108. Epub 2011 Feb 22.