Interactions between opioid agonists and glutamate receptor antagonists Public Deposited

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  • March 21, 2019
Creator
  • Fischer, Bradford D.
    • Affiliation: College of Arts and Sciences, Department of Psychology and Neuroscience
Abstract
  • The following studies systematically examine the interactive effects of opioids and glutamate receptor antagonists in assays of schedule-controlled responding and thermal nociception. Experiment 1 examines the effects of morphine, buprenorphine, butorphanol, and nalbuphine alone and in combination with an N-Methyl-D-Aspartate (NMDA) receptor antagonist on schedule-controlled responding and thermal nociception. The results from this study indicate that NMDA antagonist/morphine and NMDA antagonist/buprenorphine mixtures produce additive or infra-additive effects on schedule-controlled responding, whereas NMDA antagonist/butorphanol and NMDA antagonist/nalbuphine mixtures produced additive or supra-additive effects. In addition, mixtures of an NMDA antagonist in combination with morphine, buprenorphine, butorphanol, and nalbuphine produce additive or supra-additive effects on thermal nociception. Experiment 2 examines the interactive effects of morphine in combination with metabotropic glutamate (mGlu) receptor antagonists selective for mGlu1, mGlu5, and mGlu2/3 receptor subtypes on schedule-controlled responding and thermal nociception. The results from this experiment suggest that mGlu1, mGlu5, and mGlu2/3 antagonists produce additive effects when administered in combination with morphine on schedule-controlled iv responding. In contrast, mGlu1 and mGlu2/3 antagonists produced supra-additive effects with morphine when assessed on thermal nociception. Experiment 3 assesses the effects of NMDA, mGlu1, mGlu5, and mGlu2/3 receptor antagonists on the efficacy of buprenorphine and dezocine in an assay of thermal nociception. Under conditions in which buprenorphine and dezocine produce sub-maximal antinociceptive effects, these drugs are assessed after pretreatment with NMDA, mGlu1, mGlu5, and mGlu2/3 antagonists. The results from this study indicate that NMDA, mGlu1, and mGlu2/3 receptor antagonists increase the efficacy of both buprenorphine and dezocine on thermal nociception. Taken together, these experiments assessed the interactive effects of opioid receptor agonists and glutamate receptor antagonists on schedule-controlled responding and thermal nociception. The experimental results obtained from these studies suggest that these interactive effects are dependent upon factors such as the relative proportions of drugs and the experimental endpoint under study. In addition, the pharmacological affinity of the opioid and glutamate receptor antagonist being examined is an important determinant of their behavioral effects.
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  • In Copyright
Advisor
  • Dykstra, Linda A.
Degree granting institution
  • University of North Carolina at Chapel Hill
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  • Open access
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