Skip to main content

Advertisement

Log in

Differential tolerance to antinociceptive effects of µ opioids during repeated treatment with etonitazene, morphine, or buprenorphine in rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract.

Rationale: Repeated treatment experiments with high and low efficacy agonists provide critical insight into possible mechanisms underlying development of opioid tolerance. Objective: Experiments in a tail-withdrawal assay tested the hypothesis that magnitude of tolerance to antinociceptive effects is inversely related to agonist relative efficacy in rats intermittently treated with etonitazene, morphine, or buprenorphine. Methods: The antinociceptive effects of five µ opioid agonists were tested in male, Sprague-Dawley rats in a warm-water tail-withdrawal assay. To induce tolerance, escalating doses of the higher efficacy agonist etonitazene, the high efficacy agonist morphine, or the lower efficacy agonist buprenorphine were administered twice daily for 2–8 weeks. Results: Etonitazene, etorphine, morphine, buprenorphine, and GPA 1657 [(1)-β-2′-hydroxy-2,9-dimethyl-5-phenyl-6,7-benzomorphan] produced dose-dependent increases in tail-withdrawal latency until 100% maximum possible effect (%MPE) was obtained. Treatment with escalating doses of etonitazene, morphine, or buprenorphine produced greater tolerance to the lower efficacy agonists buprenorphine and GPA 1657 than to the higher efficacy agonists etonitazene, etorphine, and morphine. Treatment with buprenorphine, a lower efficacy agonist, produced greater tolerance than did treatment with equivalent doses of the higher efficacy agonists morphine or etonitazene. Conclusions: Taken together, these data suggest that magnitude of antinociceptive tolerance is inversely related to relative efficacy of µ agonists, with lower efficacy agonists being more susceptible to tolerance than are higher efficacy agonists under these intermittent dosing conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Author information

Authors and Affiliations

Authors

Additional information

Electronic Publication

Rights and permissions

Reprints and permissions

About this article

Cite this article

Walker, E., Young, A. Differential tolerance to antinociceptive effects of µ opioids during repeated treatment with etonitazene, morphine, or buprenorphine in rats. Psychopharmacology 154, 131–142 (2001). https://doi.org/10.1007/s002130000620

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s002130000620

Navigation