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Related Experiment Videos

Decrease in delta-opioid receptor density in rat brain after chronic [D-Ala2,D-Leu5]enkephalin treatment.

P L Tao1, L R Chang, P Y Law

  • 1Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.

Brain Research
|October 18, 1988
PubMed
Summary
This summary is machine-generated.

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Chronic treatment with [D-Ala2,D-Leu5]enkephalin (DADLE) caused tolerance by down-regulating delta-opioid receptors in rat brains. This peptide-specific receptor reduction occurred rapidly in the midbrain and striatum.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Opioid peptides like DADLE are crucial for pain modulation.
  • Chronic opioid administration can lead to tolerance, reducing drug efficacy.
  • Understanding opioid receptor regulation is key to managing pain and addiction.

Purpose of the Study:

  • To investigate the effects of chronic [D-Ala2,D-Leu5]enkephalin (DADLE) treatment on opioid receptor binding in rat brain regions.
  • To determine if DADLE causes tolerance through receptor down-regulation.
  • To examine the time course and selectivity of DADLE's effects on delta- and mu-opioid receptors.

Main Methods:

  • Chronic administration of DADLE to Sprague-Dawley rats.
  • Measurement of [3H]diprenorphine and [3H]DADLE binding to brain membranes.

Related Experiment Videos

  • Scatchard analysis to determine receptor binding kinetics (Bmax and Kd).
  • Assessment of mu-opioid receptor binding in the presence of morphiceptin.

    • Main Results:

    • Chronic DADLE treatment led to tolerance to its antinociceptive effects.
    • Significant time-dependent decreases in [3H]diprenorphine binding (delta-opioid receptors) were observed in the cortex, midbrain, and striatum.
    • Scatchard analysis indicated a decrease in Bmax values, signifying receptor down-regulation.
    • Delta-opioid receptor down-regulation in the midbrain occurred rapidly, within 6 hours of DADLE initiation.
    • Mu-opioid receptor binding decreased only in the striatum after 5 days of DADLE treatment.

    Conclusions:

    • Chronic DADLE treatment preferentially down-regulates delta-opioid receptors, similar to how chronic etorphine down-regulates mu-opioid receptors.
    • This receptor-specific down-regulation is the likely mechanism underlying DADLE-induced tolerance.
    • The findings highlight the differential regulation of opioid receptor subtypes by specific opioid peptides.