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- Title
The effects of mitragynine and morphine on schedule-controlled responding and antinociception in rats.
- Authors
Hiranita, Takato; Leon, Francisco; Felix, Jasmine S.; Restrepo, Luis F.; Reeves, Morgan E.; Pennington, Anna E.; Obeng, Samuel; Avery, Bonnie A.; McCurdy, Christopher R.; McMahon, Lance R.; Wilkerson, Jenny L.
- Abstract
Rationale: Mitragyna speciosa (kratom) may hold promise as both an analgesic and treatment for opioid use disorder. Mitragynine, its primary alkaloid constituent, is an opioid receptor ligand. However, the extent to which the in vivo effects of mitragynine are mediated by opioid receptors, or whether mitragynine interacts with other opioid agonists, is not fully established. Objectives: The effects of mitragynine and the prototypical opioid agonist morphine were compared for their capacity to decrease operant responding for food delivery, and to increase response latency to a thermal stimulus. Methods: Male and female Sprague-Dawley rats responded under a multiple cycle fixed ratio 10 schedule of food delivery and were tested on a hot plate (52 °C) immediately after each cycle. Morphine and mitragynine were administered alone, in combination with each other, and in combination with the opioid antagonist naltrexone. Results: Morphine and mitragynine dose-dependently decreased schedule-controlled responding; the ED50 values were 7.3 and 31.5 mg/kg, respectively. Both drugs increased thermal antinociception; the ED50 value for morphine was 18.3. Further, doses of naltrexone that antagonized morphine did not antagonize mitragynine. Mitragynine (17.8 mg/kg) did not alter the rate-decreasing or antinociceptive effects of morphine. Conclusions: The antinociceptive effects of mitragynine and morphine occur at doses larger than those that disrupt learned behavior. Opioid receptors do not appear to mediate the disruptive effects of mitragynine on learned behavior. Mitragynine had lesser antinociceptive effects than morphine, and these did not appear to be mediated by opioid receptors. The pharmacology of mitragynine includes a substantial non-opioid mechanism.
- Subjects
OPIOID receptors; NALTREXONE; MORPHINE; REACTION time; RATS; PHARMACOLOGY
- Publication
Psychopharmacology, 2019, Vol 236, Issue 9, p2725
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-019-05247-7