Chronic morphine treatment alters N-methyl-D-aspartate receptors in freshly isolated neurons from nucleus accumbens.

1. J Pharmacol Exp Ther. 2004 Oct;311(1):265-73. Epub 2004 Jul 19.

Chronic morphine treatment alters N-methyl-D-aspartate receptors in freshly
isolated neurons from nucleus accumbens.

Martin G(1), Guadaño-Ferraz A, Morte B, Ahmed S, Koob GF, De Lecea L, Siggins GR.

Author information:
(1)Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA,
USA.

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.

DOI: 10.1124/jpet.104.067504
PMID: 15263066 [Indexed for MEDLINE]

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