Effects of Veterinary Anesthetic Xylazine on Locomotor Activity, Exploration, and Conditioned Preference Alone and in Combination with Fentanyl in Mice

Abstract ID 94511 Poster Board 306 Xylazine, an α₂-adrenoreceptor agonist, is being used as an adulterant in the opioid supply, prominently with the potent μ opioid receptor agonist, fentanyl. Although this is a current complication being witnessed around the nation, little is known about the pharmacologic effects of the combination. Using a three-chamber conditioned place preference apparatus we conditioned Swiss-Webster mice to associate stimuli present in the black chamber with the respective drug and the white chamber with saline. During preconditioning, mice were allowed free access throughout the three chambers (black, grey, and white) prior to conditioning experiments. Ten days of conditioning were completed by injecting the mice with either drug or saline IP and placing them in one chamber for 25 minutes with alternating drug and saline days. Fentanyl produced a dose dependent increase in both preference and movement over the course of the experiment. Fentanyl also decreased the exploration behavior of the mice for the white chamber, indicating the preference for the black chamber after conditioning. On the contrary, xylazine produced a dose dependent decrease in movement in addition to producing a CPP score less than zero at each dose. Xylazine decreased exploration behavior of the mice for the black chamber, suggesting avoidance behavior. Xylazine, when administered concomitantly with fentanyl, decreased the rewarding effects of fentanyl as seen by a decrease in CPP scores. However, xylazine failed to alter the locomotor activity of the mice when given in conjunction with fentanyl and the movement results are similar to that of fentanyl alone. The combination of the two agonists revealed decreases of exploration behavior for the black chamber further expressing xylazine's reduction of fentanyl's rewarding effects. While fentanyl is a μ opioid receptor agonist and xylazine is an α₂-adrenoreceptor agonist, the combination of the two agonists may have possible pharmacologic effects on other pathways to alter rewarding effects, exploration behavior, and basic locomotion. This research was supported by the Peter F. McManus Charitable Trust.