NG-Nitro-L-arginine prevents morphine tolerance

Yuri A. Kolesnikov, Chaim G. Pick, Gavril W. Pasternak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

176 Scopus citations

Abstract

NMDA receptor antagonists, such as MK-801, prevent the development of tolerance to morphine. Since many NMDA actions involve the production of nitric oxide, we examined the effects of a nitric oxide synthase inhibitor on morphine tolerance. The analgesic response to morphine (5 mg/kg s.c.) given daily diminishes from 60% in naive animals to 0% within 5 days. Coadministration of NG-nitro-L-arginine (8 mg/kg per day) along with morphine prevents the demonstration of appreciable tolerance for at least 11 days. These results suggest that morphine tolerance involves the activation of NMDA receptors followed by the subsequent release of nitric oxide.

Original languageEnglish
Pages (from-to)399-400
Number of pages2
JournalEuropean Journal of Pharmacology
Volume221
Issue number2-3
DOIs
StatePublished - 20 Oct 1992
Externally publishedYes

Funding

FundersFunder number
Ethel Cohen Fellowship Fund
National Institute on Drug Abuse417147, R37DA007242

    Keywords

    • NMDA receptor antagonists
    • NO synthase
    • Nitric oxide (NO)

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