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Nucleus accumbens NMDA receptor subunit expression and function is enhanced in morphine-dependent rats.
Eur J Pharmacol. 2007 May 21; 562(3):191-7.EJ

Abstract

We have previously shown, using radioligand binding studies, that N-methyl-d-aspartate (NMDA) NR1 and NR2A receptor subunits density was decreased in the forebrain of morphine-dependent rats. We have now determined if morphine-dependent rats display regional differences in NMDA receptor expression and whether such changes are functionally relevant. In morphine-dependent rats, the expression of NR1 and NR2A subunits protein, as determined by Western blotting with NMDA receptor subunit antibodies, were decreased in frontal cortex and hippocampus but significantly increased in the nucleus accumbens. The expression of the NR2B subunit was unchanged in all regions examined. In separate groups of morphine-dependent rats, MK-801-induced hyperactivity (thought to be mediated via modulation of nucleus accumbens dopamine release) was significantly enhanced in morphine-dependent animals. Similarly, the MK-801-induced increase of dopamine metabolism was significantly increased in the nucleus accumbens of morphine-dependent animals as compared to sham controls. Results provide both biochemical and behavioural evidence to suggest that NMDA receptor function in the nucleus accumbens, at least with respect to an interaction with the limbic dopamine system, is markedly enhanced in morphine-dependent rats. This increase in function may be associated with an enhanced expression of NMDA receptors, particularly those in the nucleus accumbens containing the NR2A subunit. Taken together, these data support several studies in the literature indicating that NMDA receptors in the nucleus accumbens are involved in the process of opiate dependence.

Authors+Show Affiliations

AstraZeneca, Alderley Park, Macclesfiled, Cheshire, SK10 4TG, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17321516

Citation

Murray, Fraser, et al. "Nucleus Accumbens NMDA Receptor Subunit Expression and Function Is Enhanced in Morphine-dependent Rats." European Journal of Pharmacology, vol. 562, no. 3, 2007, pp. 191-7.
Murray F, Harrison NJ, Grimwood S, et al. Nucleus accumbens NMDA receptor subunit expression and function is enhanced in morphine-dependent rats. Eur J Pharmacol. 2007;562(3):191-7.
Murray, F., Harrison, N. J., Grimwood, S., Bristow, L. J., & Hutson, P. H. (2007). Nucleus accumbens NMDA receptor subunit expression and function is enhanced in morphine-dependent rats. European Journal of Pharmacology, 562(3), 191-7.
Murray F, et al. Nucleus Accumbens NMDA Receptor Subunit Expression and Function Is Enhanced in Morphine-dependent Rats. Eur J Pharmacol. 2007 May 21;562(3):191-7. PubMed PMID: 17321516.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nucleus accumbens NMDA receptor subunit expression and function is enhanced in morphine-dependent rats. AU - Murray,Fraser, AU - Harrison,Neil J, AU - Grimwood,Sarah, AU - Bristow,Linda J, AU - Hutson,Peter H, Y1 - 2007/01/30/ PY - 2006/06/19/received PY - 2007/01/08/revised PY - 2007/01/10/accepted PY - 2007/2/27/pubmed PY - 2007/6/22/medline PY - 2007/2/27/entrez SP - 191 EP - 7 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 562 IS - 3 N2 - We have previously shown, using radioligand binding studies, that N-methyl-d-aspartate (NMDA) NR1 and NR2A receptor subunits density was decreased in the forebrain of morphine-dependent rats. We have now determined if morphine-dependent rats display regional differences in NMDA receptor expression and whether such changes are functionally relevant. In morphine-dependent rats, the expression of NR1 and NR2A subunits protein, as determined by Western blotting with NMDA receptor subunit antibodies, were decreased in frontal cortex and hippocampus but significantly increased in the nucleus accumbens. The expression of the NR2B subunit was unchanged in all regions examined. In separate groups of morphine-dependent rats, MK-801-induced hyperactivity (thought to be mediated via modulation of nucleus accumbens dopamine release) was significantly enhanced in morphine-dependent animals. Similarly, the MK-801-induced increase of dopamine metabolism was significantly increased in the nucleus accumbens of morphine-dependent animals as compared to sham controls. Results provide both biochemical and behavioural evidence to suggest that NMDA receptor function in the nucleus accumbens, at least with respect to an interaction with the limbic dopamine system, is markedly enhanced in morphine-dependent rats. This increase in function may be associated with an enhanced expression of NMDA receptors, particularly those in the nucleus accumbens containing the NR2A subunit. Taken together, these data support several studies in the literature indicating that NMDA receptors in the nucleus accumbens are involved in the process of opiate dependence. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17321516/Nucleus_accumbens_NMDA_receptor_subunit_expression_and_function_is_enhanced_in_morphine_dependent_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00096-9 DB - PRIME DP - Unbound Medicine ER -