PMID- 15263066
OWN - NLM
STAT- MEDLINE
DCOM- 20041215
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 311
IP  - 1
DP  - 2004 Oct
TI  - Chronic morphine treatment alters N-methyl-D-aspartate receptors in freshly 
      isolated neurons from nucleus accumbens.
PG  - 265-73
AB  - Although there is now evidence of a role for N-methyl-D-aspartate (NMDA) 
      receptors in nucleus accumbens (NAcc) neurons in the effects of chronic opiate 
      treatment, the cellular and molecular mechanisms underlying this phenomenon are 
      still unclear. Therefore, we studied the effects of chronic morphine on the 
      pharmacological and biophysical properties of NMDA receptors in freshly isolated 
      medium spiny neurons from NAcc. We found that chronic morphine treatment did not 
      alter the affinity for NMDA receptor agonists such as glutamate, homoquinolinic 
      acid, and NMDA, but decreased the affinity of glycine, the allosteric NMDA 
      receptor coagonist, from 2.24 +/- 0.15 microM to 5.1 +/- 1.45 microM. Chronic 
      morphine treatment also altered the affinity of two noncompetitive NMDA receptor 
      antagonists, 7-chloro-kynurenic acid and ifenprodil. However, morphine had no 
      effect on a third antagonist, D-(-)-2-amino-5-phosphonopentanoic acid. 
      Single-exponential fits of desensitized NMDA current tails gave tau values 
      ranging from 0.5 to 4 s in neurons from both control and morphine-treated rats. 
      However, a shift to the left of the distribution of tau values after morphine 
      treatment revealed that NMDA current desensitization rate was accelerated in a 
      majority of NAcc neurons. Taken together with our recent molecular studies, our 
      data are consistent with a shift away from NMDA receptor subunit (NR) NR2B and 2C 
      function toward increased NR2A subunit expression or function after chronic 
      morphine, a process that could alter excitability and integrative properties and 
      may represent a neuroadaptation of NAcc medium spiny neurons underlying morphine 
      dependence.
FAU - Martin, Gilles
AU  - Martin G
AD  - Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA, 
      USA. gilles.martin@umassmed.edu
FAU - Guadano-Ferraz, Ana
AU  - Guadano-Ferraz A
FAU - Morte, Beatriz
AU  - Morte B
FAU - Ahmed, Serge
AU  - Ahmed S
FAU - Koob, George F
AU  - Koob GF
FAU - De Lecea, Luis
AU  - De Lecea L
FAU - Siggins, George R
AU  - Siggins GR
LA  - eng
GR  - AA06420/AA/NIAAA NIH HHS/United States
GR  - DA03665/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040719
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 76I7G6D29C (Morphine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Analgesics, Opioid/pharmacology
MH  - Animals
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Glycine/metabolism
MH  - Morphine/*pharmacology
MH  - Neurons/*drug effects/metabolism
MH  - Nucleus Accumbens/*cytology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/drug effects/*metabolism
EDAT- 2004/07/21 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/07/21 05:00
PHST- 2004/07/21 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/07/21 05:00 [entrez]
AID - jpet.104.067504 [pii]
AID - 10.1124/jpet.104.067504 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2004 Oct;311(1):265-73. doi: 10.1124/jpet.104.067504. Epub 
      2004 Jul 19.