Effect of Peripheral μ-, δ-, and κ-Opioid Ligands on the Development of Tolerance to Ethanol-Induced Analgesia

We studied the rate of development of tolerance to the ethanol-induced analgesia under the effect of mu-, delta-, and kappa-opioid agonists and antagonists not crossing the blood-brain barrier and rapidly inactivated by gastric and duodenal proteolytic enzymes. Activation of gastric kappa-opioid receptors eliminated the analgesic effect of ethanol and accelerated the development of tolerance to ethanol-induced analgesia. In contrast, activation of gastric mu-opioid receptors decelerated the development of this tolerance. Activation of gastric delta-opioid receptors produced no effect on examined tolerance. mu-Opioid receptor antagonist decelerated and delta-opioid receptor antagonist accelerated the development of tolerance to ethanol-induced analgesia. Thus, the state of gastric opioid receptors affects the manifestation of ethanol-induced analgesia and the development of tolerance to this effect.