TY - JOUR
T1 - Modulation of NMDA receptor subunit mRNA in butorphanol-tolerant and-withdrawing rats
AU - Oh, Seikwan
AU - Kim, Joo Il
AU - Chung, Myeon Woo
AU - Ho, Ing K.
N1 - Funding Information:
This study was supported by a research grant from KFDA (2000).
PY - 2000
Y1 - 2000
N2 - The NMDA receptor has been implicated in opioid tolerance and withdrawal. The effects of continuous infusion of butorphanol on the modulation of NMDA receptor subunit NR1, NR2A, NR2B, and NR2C gene expression were investigated by using in situ hybridization technique. Continuous intracerebroventricular (i.c.v.) infusion with butorphanol (26 nmol/μl/h) resulted in significant modulations in the NR1, NR2A, and NR2B mRNA levels. The Bevel of NR1 mRNA was significantly decreased in the cerebral cortex, thalamus, and CA1 area of hippocampus in butorphanol tolerant and withdrawal 17 h after stopping the infusion) rats. The NR2A mRNA was significantly decreased in the CA1 and CA3 of hippocampus in tolerant rats and increased in the cerebral cortex and dentate gyrus in butorphanol withdrawal rats. NR2B subunit mRNA was decreased in the cerebral cortex, caudate putamen, thalamus, CA3 of hippocampus in butorphanol withdrawal rats. No changes of NR1, NR2A, NR2C subunit mRNA in the cerebellar granule cell layer were observed in either butorphanol tolerant or withdrawal rats. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased significantly in all brain regions except in the thalamus and hippocampus, at the 7 hr after stopping the butorphanol infusion. These results suggest that region-specific changes of NMDA receptor subunit mRNA (NR1 and NR2) as well as NMDA receptor binding ([3H]MK-801 are involved in the development of tolerance to and withdrawal from butorphanol.
AB - The NMDA receptor has been implicated in opioid tolerance and withdrawal. The effects of continuous infusion of butorphanol on the modulation of NMDA receptor subunit NR1, NR2A, NR2B, and NR2C gene expression were investigated by using in situ hybridization technique. Continuous intracerebroventricular (i.c.v.) infusion with butorphanol (26 nmol/μl/h) resulted in significant modulations in the NR1, NR2A, and NR2B mRNA levels. The Bevel of NR1 mRNA was significantly decreased in the cerebral cortex, thalamus, and CA1 area of hippocampus in butorphanol tolerant and withdrawal 17 h after stopping the infusion) rats. The NR2A mRNA was significantly decreased in the CA1 and CA3 of hippocampus in tolerant rats and increased in the cerebral cortex and dentate gyrus in butorphanol withdrawal rats. NR2B subunit mRNA was decreased in the cerebral cortex, caudate putamen, thalamus, CA3 of hippocampus in butorphanol withdrawal rats. No changes of NR1, NR2A, NR2C subunit mRNA in the cerebellar granule cell layer were observed in either butorphanol tolerant or withdrawal rats. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased significantly in all brain regions except in the thalamus and hippocampus, at the 7 hr after stopping the butorphanol infusion. These results suggest that region-specific changes of NMDA receptor subunit mRNA (NR1 and NR2) as well as NMDA receptor binding ([3H]MK-801 are involved in the development of tolerance to and withdrawal from butorphanol.
KW - Autoradiography
KW - In situ hybridization
KW - NMDA receptor
KW - Withdrawal
UR - http://www.scopus.com/inward/record.url?scp=0034527097&partnerID=8YFLogxK
U2 - 10.1023/A:1026618603795
DO - 10.1023/A:1026618603795
M3 - Article
C2 - 11152389
AN - SCOPUS:0034527097
SN - 0364-3190
VL - 25
SP - 1603
EP - 1611
JO - Neurochemical Research
JF - Neurochemical Research
IS - 12
M1 - 293315
ER -