Region specific expression of NMDA receptor NR1 subunit mRNA in hypothalamus and pons following chronic morphine treatment.
The NMDA receptor has been implicated in opioid tolerance and physical dependence. Using in situ hybridization techniques, the effects of chronic morphine treatment on the expression of mRNAs encoding the NMDA receptor subunits NRI, NR2A, and NR2B were investigated. A significant increase in the level of the NR1 subunit mRNA was found in the locus coeruleus and the hypothalamic paraventricular nucleus following 3 days of intracerebroventricular (i.c.v.) morphine infusion (26 nmol microl(-1) h(-1)) through osmotic minipumps. No changes were detected in expression of the NRI mRNA in the frontal cortex, caudate-putamen, nucleus accumbens, amygdala, CA1, CA2, and the dentate gyrus of the hippocampus, and in the central grey after morphine treatment. The expression of NR2A and NR2B subunit mRNAs did not change after morphine treatment in any brain region. These results suggest that changes in gene expression of the NRI subunit of the NMDA receptor are involved in the development of morphine tolerance and dependence.
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505, USA.
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D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D004027:Diencephalon / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D011149:Pons / Q000187:drug effects* / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*