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Related Experiment Videos

Cynomolgus monkeys do not develop tolerance to opioids.

J W Ternes, R Ehrman, C P O'Brien

    Behavioral Neuroscience
    |April 1, 1983
    PubMed
    Summary
    This summary is machine-generated.

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    Rhesus monkeys developed tolerance and physical dependence on opioids, while closely related cynomolgus monkeys did not. This suggests a potential genetic basis for opioid tolerance and dependence.

    Area of Science:

    • Pharmacology
    • Neuroscience
    • Genetics

    Background:

    • Opioid tolerance and physical dependence are significant challenges in pain management.
    • Understanding the mechanisms underlying these phenomena is crucial for developing safer analgesics.
    • Species-specific differences in drug response can provide insights into underlying genetic factors.

    Purpose of the Study:

    • To investigate the development of tolerance to the opioid hydromorphone in two species of non-human primates.
    • To compare the development of opioid tolerance and physical dependence between rhesus and cynomolgus monkeys.
    • To explore the potential genetic basis for differential responses to sustained opioid administration.

    Main Methods:

    • Eight cynomolgus and two rhesus monkeys were trained for lever pressing to receive food reinforcement.

    Related Experiment Videos

  • Monkeys were catheterized for intravenous hydromorphone infusions.
  • Three doses of hydromorphone and six interdose intervals were studied.
  • Behavioral suppression of lever pressing was monitored.
  • Naloxone challenges were administered to assess physical dependence.

    • Main Results:

    • Hydromorphone initially suppressed lever pressing in both species.
    • Rhesus monkeys acquired tolerance to hydromorphone's sedative effects after 14 exposures.
    • Cynomolgus monkeys did not acquire tolerance even after over 100 exposures.
    • Rhesus monkeys exhibited withdrawal symptoms upon naloxone challenge, while cynomolgus monkeys did not.

    Conclusions:

    • Significant species-specific differences exist in the development of tolerance and physical dependence on hydromorphone.
    • The failure of cynomolgus monkeys to develop tolerance or dependence suggests a potential genetic influence.
    • These findings highlight the importance of genetic factors in opioid response and may inform future research into opioid pharmacogenetics.