@article {Minervinijpet.116.235630, author = {Vanessa Minervini and Sujata S Dahal and Charles France}, title = {Behavioral Characterization of Kappa Opioid Receptor Agonist Spiradoline and Cannabinoid Receptor Agonist CP55940 Mixtures in Rats}, elocation-id = {jpet.116.235630}, year = {2016}, doi = {10.1124/jpet.116.235630}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Pain is a significant clinical problem and there is a need for more effective treatments with reduced adverse effects that currently limit the use of mu opioid receptor agonists. Synthetic kappa opioid receptor agonists have no abuse liability and well-documented antinociceptive effects; however, adverse effects (diuresis, dysphoria) preclude their use in the clinic. Combining kappa opioids with non-opioid drugs (cannabinoid receptor agonists) allows for smaller doses of each drug to produce antinociception. This study tested whether a potentially useful effect of the kappa opioid receptor agonist spiradoline (antinociception) is selectively enhanced by the cannabinoid receptor agonist CP55940. Cumulative dose-response functions were determined in 8 male Sprague Dawley rats for spiradoline (0.032-32.0 mg/kg, i.p.) and CP55940 (0.0032-1.0 mg/kg, i.p.) for antinociception, hypothermia, food-maintained responding, and diuresis. Alone, each drug dose-dependently increased tail withdrawal latencies from 50oC water, decreased body temperature by ~4oC, and eliminated food-maintained responding. Spiradoline but not CP55940 significantly increased urine output at doses that eliminated responding. Smaller doses of spiradoline and CP55940 in mixtures (3:1, 1:1, and 1:3 spiradoline:CP55940) had effects comparable to those observed with larger doses of either drug administered alone: the interaction was additive for antinociception and additive or greater than additive for hypothermia and food-maintained responding. Collectively these data fail to provide support for the use of these mixtures for treating acute pain; however, kappa opioid/cannabinoid mixtures might be useful for treating pain under other conditions (e.g., chronic pain), but only if the adverse effects of both drugs are not enhanced in mixtures.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/early/2016/11/30/jpet.116.235630}, eprint = {https://jpet.aspetjournals.org/content/early/2016/11/30/jpet.116.235630.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }