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Differential effects of naltrindole on morphine-induced tolerance and physical dependence in rats.

Publication ,  Journal Article
Hepburn, MJ; Little, PJ; Gingras, J; Kuhn, CM
Published in: J Pharmacol Exp Ther
June 1997

This study investigated the effect of delta opioid receptor blockade by naltrindole on the development of physical dependence and tolerance to the antinociceptive and respiratory depressive effects of morphine in rats. Chronic morphine was delivered either by s.c. injection of increasing amounts of morphine over 5 days or by s.c. implantation of morphine pellets. Animals were cotreated with saline or naltrindole. Antinociception and respiratory depression were assessed after administration of a challenge dose of morphine, and withdrawal signs were determined after naloxone challenge. Naltrindole significantly attenuated the development of antinociceptive tolerance after all three chronic treatment regimens. In addition, rats pretreated with naltrindole displayed significantly fewer withdrawal symptoms and less weight loss after a naloxone challenge. In contrast, naltrindole did not prevent the development of tolerance to morphine-induced respiratory depression. These results imply that tolerance to antinociception and physical dependence involves adaptations at interacting mu and delta receptor populations, whereas tolerance to respiratory depression reflects actions of independent mu and delta receptor populations. These findings suggest that delta antagonists may have potential clinical application for decreasing the rapid development of tolerance to opiate-induced analgesia, while allowing for the development of protective tolerance to respiratory depression.

Duke Scholars

Published In

J Pharmacol Exp Ther

ISSN

0022-3565

Publication Date

June 1997

Volume

281

Issue

3

Start / End Page

1350 / 1356

Location

United States

Related Subject Headings

  • Substance-Related Disorders
  • Rats, Sprague-Dawley
  • Rats
  • Pharmacology & Pharmacy
  • Narcotic Antagonists
  • Naltrexone
  • Morphine
  • Male
  • Female
  • Drug Tolerance
 

Citation

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Hepburn, M. J., Little, P. J., Gingras, J., & Kuhn, C. M. (1997). Differential effects of naltrindole on morphine-induced tolerance and physical dependence in rats. J Pharmacol Exp Ther, 281(3), 1350–1356.
Hepburn, M. J., P. J. Little, J. Gingras, and C. M. Kuhn. “Differential effects of naltrindole on morphine-induced tolerance and physical dependence in rats.J Pharmacol Exp Ther 281, no. 3 (June 1997): 1350–56.
Hepburn MJ, Little PJ, Gingras J, Kuhn CM. Differential effects of naltrindole on morphine-induced tolerance and physical dependence in rats. J Pharmacol Exp Ther. 1997 Jun;281(3):1350–6.
Hepburn, M. J., et al. “Differential effects of naltrindole on morphine-induced tolerance and physical dependence in rats.J Pharmacol Exp Ther, vol. 281, no. 3, June 1997, pp. 1350–56.
Hepburn MJ, Little PJ, Gingras J, Kuhn CM. Differential effects of naltrindole on morphine-induced tolerance and physical dependence in rats. J Pharmacol Exp Ther. 1997 Jun;281(3):1350–1356.

Published In

J Pharmacol Exp Ther

ISSN

0022-3565

Publication Date

June 1997

Volume

281

Issue

3

Start / End Page

1350 / 1356

Location

United States

Related Subject Headings

  • Substance-Related Disorders
  • Rats, Sprague-Dawley
  • Rats
  • Pharmacology & Pharmacy
  • Narcotic Antagonists
  • Naltrexone
  • Morphine
  • Male
  • Female
  • Drug Tolerance