Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 186 (2), 177-84

Development of Tolerance and Sensitization to Different Opioid Agonists in Rats

Affiliations

Development of Tolerance and Sensitization to Different Opioid Agonists in Rats

Gisela Grecksch et al. Psychopharmacology (Berl).

Abstract

Rationale: Despite numerous investigations, the mechanisms underlying the development of opioid tolerance are far from clear. However, several in vitro studies implicated a protective role of agonist-induced micro-opioid receptor endocytosis in the development of opioid tolerance. Moreover, we have recently demonstrated that the high-efficacy agonist etonitazene promotes rapid endocytosis of micro-opioid receptors, whereas the agonist morphine and the low-efficacy agonist buprenorphine fail to promote detectable receptor endocytosis in micro-opioid receptor expressing HEK293 cells.

Objectives: The present study explored the effects of these opioids on the development of tolerance and sensitization in rats in vivo.

Methods: The opioid effects were quantified using the hot plate, electric tail root stimulation, and the locomotor activity chamber in male Wistar rats. Dose-response curves were generated for each test drug. To induce tolerance, equieffective doses of etonitazene, morphine, and buprenorphine were administered daily for 29 days.

Results: We found that chronic treatment with the non-internalizing drugs buprenorphine and morphine resulted in a greater development of tolerance than etonitazene. In addition, the sensitization to the locomotor stimulant effect was high after buprenorphine and morphine, but was lacking after chronic etonitazene application.

Conclusion: The results support a role for the endocytotic potency of agonists in the development of tolerance and addiction during long-term opioid treatment.

Similar articles

See all similar articles

Cited by 32 articles

See all "Cited by" articles

References

    1. Neurosci Biobehav Rev. 2004 Jan;27(8):777-86 - PubMed
    1. Rev Med Chir Soc Med Nat Iasi. 2001 Jul-Sep;105(3):444-50 - PubMed
    1. Life Sci. 1993;52(18):PL199-203 - PubMed
    1. Mol Pharmacol. 1995 Apr;47(4):848-54 - PubMed
    1. J Biol Chem. 2001 Aug 17;276(33):31408-14 - PubMed

LinkOut - more resources

Feedback