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Related Experiment Videos

Morphine tolerance increases mu-noncompetitive delta binding sites.

R B Rothman, J A Danks, A E Jacobson

    European Journal of Pharmacology
    |May 13, 1986
    PubMed
    Summary
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    Chronic morphine use selectively increases specific opioid receptors in the brain, potentially explaining morphine tolerance and physical dependence. This study highlights changes in lower affinity binding sites.

    Area of Science:

    • Neuropharmacology
    • Molecular Biology
    • Addiction Research

    Background:

    • Endogenous opioid peptides and their receptors are crucial for pain modulation and reward pathways.
    • Morphine tolerance and physical dependence are complex phenomena involving alterations in opioid receptor systems.
    • Previous studies have suggested changes in opioid receptor binding with chronic morphine exposure.

    Purpose of the Study:

    • To reevaluate the effects of chronic morphine administration on opioid receptor binding parameters.
    • To investigate the specific changes in receptor subtypes and their affinities associated with morphine tolerance.

    Main Methods:

    • Rats were administered morphine or placebo via implanted pellets.
    • Brain membranes were labeled using [3H][D-Ala2,D-Leu5]enkephalin ([3H]DADL) as a ligand.

    Related Experiment Videos

  • Binding surface analysis and Scatchard plots were employed, with and without the selective alkylating agent FIT (N-phenyl-N-[1-(2-p-isothiocyanato)phenyl-ethyl)-4-piperidinyl] propanamide).

    • Main Results:

    • A 47% selective up-regulation of lower affinity [3H]DADL binding sites (identified as mu-noncompetitive delta binding sites) was observed in morphine-treated rats.
    • FIT-treated membranes, enriched in these lower affinity sites, showed a 60-65% up-regulation after chronic morphine treatment.
    • These findings indicate a specific alteration in a subpopulation of opioid receptors.

    Conclusions:

    • Chronic morphine administration selectively alters a specific subpopulation of opioid receptors.
    • The up-regulation of mu-noncompetitive delta binding sites may be a key mechanism underlying opiate tolerance and physical dependence.
    • Further research into these specific receptor alterations could inform strategies for managing opioid use disorder.