Region specific expression of NMDA receptor NR1 subunit mRNA in hypothalamus and pons following chronic morphine treatment

• Published in: European journal of pharmacology Vol. 365; no. 1; pp. 47 - 54
• Main Authors: Zhu, Hong, Jang, Choon-Gon, Ma, Tangeng, Oh, Seikwan, Rockhold, Robin W, Ho, Ing K
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15-01-1999; Elsevier
• Subjects: Analgesics, Opioid - pharmacology; Animals; Biological and medical sciences; Brain Stem - drug effects; Brain Stem - metabolism; Diencephalon - drug effects; Diencephalon - metabolism; Drug toxicity and drugs side effects treatment; Gene Expression Regulation - drug effects; Hippocampus - drug effects; Hippocampus - metabolism; Hypothalamus - drug effects; Hypothalamus - metabolism; In Situ Hybridization; Male; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Morphine; Morphine - pharmacology; NMDA receptor; Pharmacology. Drug treatments; Physical dependence; Pons - drug effects; Pons - metabolism; Prosencephalon - drug effects; Prosencephalon - metabolism; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - genetics; RNA, Messenger - genetics; Tolerance; Tolerance; Morphine; Physical dependence; NMDA receptor; In situ hybridization; Rat; Toxicity; Rodentia; Opiates; Glutamate receptor; Cerebral ventricle; Narcotic analgesic; Gene expression; Vertebrata; Mammalia; Messenger RNA; Animal; Dependence; Intracerebral administration; Mechanism of action
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00861-9

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 NR1, 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 μl
−1 h
−1) through osmotic minipumps. No changes were detected in expression of the NR1 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 NR1 subunit of the NMDA receptor are involved in the development of morphine tolerance and dependence.