Related Experiment Videos
Morphine antagonizes U50,488's effects in a squirrel monkey shock titration procedure
1Department of Psychology, University of North Carolina, Chapel Hill 27599-3270.
Abstract:
To determine whether a mu opioid agonist modulates the effects of a kappa opioid agonist in squirrel monkeys responding under a shock titration procedure, morphine was administered in combination with an ED75 dose of U50,488. Morphine (0.03-0.3 mg/kg) did not alter U50,488's early peak effects (15-25 min post-injection), but dose dependently antagonized U50,488's later effects (40-100 min post-injection); these doses of morphine shifted the U50,488 dose-effect curve < 1/4 log unit to the right. After 6-8 weeks of daily morphine administration, higher doses of morphine (0.3-3.0 mg/kg) shifted the U50,488 dose-effect curve > 1/2 log unit to the right. Morphine still did not antagonize early peak effects of the ED75 dose of U50,488, but antagonized early and late effects of a lower dose. Thus, morphine is a weak kappa antagonist in the shock titration procedure. In addition to its low affinity for kappa receptors, morphine's kappa antagonist activity is limited by its mu agonist effects, particularly in the non-morphine-tolerant monkey.
Insights
Morphine, a mu opioid agonist, weakly antagonizes kappa opioid effects in squirrel monkeys. This antagonism is dose-dependent and influenced by morphine tolerance, suggesting complex opioid interactions.
Area of Science:
- Pharmacology
- Neuroscience
- Behavioral Science
Background:
- Opioid agonists interact with specific receptors, influencing physiological and behavioral responses.
- Understanding opioid interactions is crucial for pain management and addiction research.
Purpose of the Study:
- To investigate the modulatory effects of a mu opioid agonist (morphine) on a kappa opioid agonist (U50,488) in a squirrel monkey model.
- To assess the impact of morphine tolerance on these opioid interactions.
Main Methods:
- Squirrel monkeys were subjected to a shock titration procedure.
- Morphine was administered alone and in combination with U50,488.
- Dose-effect curves for U50,488 were analyzed before and after chronic morphine administration.
Main Results:
- Acute morphine administration showed dose-dependent antagonism of later U50,488 effects, but not early peak effects.
- Chronic morphine administration resulted in a greater rightward shift of the U50,488 dose-effect curve.
- Morphine demonstrated weak kappa antagonist activity, particularly in non-tolerant monkeys.
Conclusions:
- Morphine exhibits weak kappa antagonist properties in the shock titration procedure.
- Morphine's mu agonist activity and tolerance development influence its kappa antagonist efficacy.
- These findings highlight the complex interplay between mu and kappa opioid receptor systems.