Document Detail

Morphine tolerance increases [3H]MK-801 binding affinity and constitutive neuronal nitric oxide synthase expression in rat spinal cord.
MedLine Citation:
PMID:  11064618     Owner:  NLM     Status:  MEDLINE    
N-Methyl-D-aspartate (NMDA) receptor antagonists and nitric oxide synthase (NOS) inhibitors inhibit morphine tolerance. In the present study, a lumbar subarachnoid polyethylene (PE10) catheter was implanted for drug administration to study alterations in NMDA receptor activity and NOS protein expression in a morphine-tolerant rat spinal model. Antinociceptive tolerance was induced by intrathecal (i.t.) morphine infusion (10 micrograms h-1) for 5 days. Co-administered (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) (10 micrograms h-1 i.t.) with morphine was used to inhibit the development of morphine tolerance. Lumbar spinal cord segments were removed and prepared for [3H]MK-801 binding assays and NOS western blotting. The binding affinity of [3H]MK-801 was higher in spinal cords of morphine-tolerant rats (mean (SEM) KD = 0.41 (0.09) nM) than in control rats (1.50 (0.13) nM). There was no difference in Bmax. Western blot analysis showed that constitutive expression of neuronal NOS (nNOS) protein in the morphine-tolerant group was twice that in the control group. This up-regulation was partially prevented by MK-801. The results suggest that morphine tolerance affects NMDA receptor binding activity and increases nNOS expression in the rat spinal cord.
C S Wong; M M Hsu; Y Y Chou; P L Tao; C S Tung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of anaesthesia     Volume:  85     ISSN:  0007-0912     ISO Abbreviation:  Br J Anaesth     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-11-09     Completed Date:  2000-11-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372541     Medline TA:  Br J Anaesth     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  587-91     Citation Subset:  IM    
Department of Anesthesiology, National Defense Medical Center, Taipei, Taiwan.
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MeSH Terms
Analgesics, Opioid / pharmacology*
Dizocilpine Maleate / pharmacology
Drug Tolerance / physiology*
Excitatory Amino Acid Antagonists / pharmacology
Morphine / pharmacology*
Nitric Oxide Synthase / metabolism*
Nitric Oxide Synthase Type I
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors,  metabolism*
Spinal Cord / drug effects,  metabolism
Up-Regulation / drug effects
Reg. No./Substance:
0/Analgesics, Opioid; 0/Excitatory Amino Acid Antagonists; 0/Receptors, N-Methyl-D-Aspartate; 57-27-2/Morphine; 77086-22-7/Dizocilpine Maleate; EC Oxide Synthase; EC Oxide Synthase Type I; EC protein, rat

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