Facilitation of morphine-induced tolerance and physical dependence by prolyl-leucyl-glycinamide

European Journal of Pharmacology
P C Contreras, A E Takemori

Abstract

The pretreatment of mice with 30 mg/kg morphine s.c. did not alter the analgesic effect of morphine in mice pretreated with saline but decreased the analgesic effect of morphine in mice pretreated with prolyl-leucyl-glycinamide (PLG). Tolerance was evaluated by the effect of PLG on morphine-induced enhancement of naloxone potency which is a measure of the capacity of naloxone to antagonize morphine-induced analgesia and is postulated to be an indicator of tolerance development. The naloxone potency of PLG-treated mice was 2-fold greater than that of control mice. PLG did not alter the whole brain levels of morphine, nor did it alter the naloxone potency in mice which were not pretreated with 30 mg/kg morphine. In mice treated with 100 mg/kg morphine or implanted with 50 mg morphine pellets for 24 or 72 h, the amount of naloxone required to induce jumping was not altered by PLG. However, PLG treatment did increase the hypothermia and body weight loss seen after naloxone-induced withdrawal. Administration of PLG to morphine-dependent mice 1 h prior to naloxone did not modify the resultant hypothermia or body weight loss. These results indicate that PLG facilitated the development of morphine tolerance and dependence.

References

Jan 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·R WalterL B Flexner
May 1, 1979·Journal of Pharmaceutical Sciences·G L Sprague, A E Takemori
Jan 1, 1977·Psychoneuroendocrinology·J M van Ree, D de Wied
Nov 1, 1976·Life Sciences·J M van Ree, D de Wied
Jan 1, 1980·Pharmacology, Biochemistry, and Behavior·H N BhargavaR F Ritzmann

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Citations

Oct 14, 1983·European Journal of Pharmacology·G E Delander, A E Takemori
Jun 15, 1984·European Journal of Pharmacology·P C Contreras, A E Takemori
Feb 18, 1986·European Journal of Pharmacology·J R Martin, A E Takemori
Oct 1, 1982·Pharmacology, Biochemistry, and Behavior·R H EhrensingA J Kastin
Jan 1, 1983·Pharmacology & Therapeutics·W G Clark, J M Lipton
Nov 1, 1982·Peptides·G A OlsonD H Coy

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