Xylazine induced central antinociception mediated by endogenous opioids and μ-opioid receptor, but not δ-or κ-opioid receptors

Endogenous opioids have been implicated in compound-induced antinociception, and our group previously suggested that xylazine induces peripheral antinociception by releasing endogenous opioids that act on their respective receptors. In this study, we investigated the involvement of endogenous opioids in alpha(2)-adrenoceptor agonist xylazine-induced central antinociception. The nociceptive threshold for thermal stimulation was measured in Swiss mice using the tail-flick test. The drugs were administered via the intracerebroventricular route. Probabilities less than 5% (p<0.05) were considered to be statistically significant (ANOVA/Bonferroni's test). Our results demonstrated that opioid receptor antagonist naloxone and mu-opioid receptor antagonist clocinnamox, but not mu-opioid receptor antagonist naltrindole and x-opioid receptor antagonist nor-binaltorphimine, antagonized xylazine-induced central antinociception. These data provide evidence for the involvement of endogenous opioids and mu-opioid receptors in xylazine-induced central antinociception. In contrast, delta- and kappa-opioid receptors do not appear to be involved in this effect. The results contribute to a greater understanding of the central antinociceptive mechanisms of a drug widely used in veterinary therapy. (C) 2013 Elsevier B.V. All rights reserved.