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Related Experiment Videos

Acute sensitization to opioid antagonists

D White-Gbadebo1, S G Holtzman

  • 1Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322.

Pharmacology, Biochemistry, and Behavior
|March 1, 1994
PubMed
Summary
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Acute morphine pretreatment sensitizes rats to opioid antagonists, particularly those acting on mu-opioid receptors. This study confirms the mu-opioid receptor

Area of Science:

  • Pharmacology
  • Neuroscience
  • Behavioral Science

Background:

  • Opioid antagonists like naloxone and naltrexone are used to reverse opioid effects.
  • Previous research suggests morphine pretreatment can alter sensitivity to these antagonists.
  • The role of the mu-opioid receptor in this sensitization process requires further investigation.

Purpose of the Study:

  • To investigate the effects of acute morphine pretreatment on the sensitivity of rats to various opioid antagonists.
  • To determine if this sensitization is specific to mu-opioid receptor agonists.
  • To explore the stereoselectivity of morphine-induced sensitization among different opioid isomers.

Main Methods:

  • Rats were trained to respond for food reinforcement on a fixed-interval schedule.

Related Experiment Videos

  • Animals received either vehicle or morphine (3.0 mg/kg) pretreatment 4 hours before testing.
  • Opioid antagonists were administered cumulatively, and their effects on response rate were measured.

    • Main Results:

    • Morphine pretreatment significantly sensitized rats to the response rate-decreasing effects of naltrexone, naloxone, and diprenorphine.
    • The ED50 for naltrexone decreased from 20 to 0.03 mg/kg following morphine pretreatment.
    • Sensitization was stereoselective for benzomorphan isomers and observed for nalorphine but not buprenorphine or nalbuphine.

    Conclusions:

    • Acute morphine pretreatment induces a mu-opioid receptor-dependent sensitization to opioid antagonists.
    • This finding highlights the critical role of the mu-opioid receptor in the development of tolerance and altered responses to opioid antagonists.
    • The results have implications for understanding opioid receptor pharmacology and developing strategies for managing opioid effects.