Opioid-Induced Tolerance and Dependence in Mice Is Modulated by the Distance between Pharmacophores in a Bivalent Ligand Series

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 102; no. 52; pp. 19208 - 19213
• Main Authors: David J. Daniels, Natalie R. Lenard, Chris L. Etienne, Law, Ping-Yee, Sandra C. Roerig, Portoghese, Philip S.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 27.12.2005; National Acad Sciences
• Subjects: Agonists; Analgesics - pharmacology; Analgesics, Opioid - pharmacology; Animals; Biological Sciences; Chemistry, Pharmaceutical - methods; Dose-Response Relationship, Drug; Drug interactions; Drug tolerance; Lactose tolerance test; Ligands; Male; Mice; Mice, Inbred ICR; Models, Chemical; Models, Statistical; Morphine; Morphine - pharmacology; Morphine dependence; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Narcotics; Narcotics - metabolism; Opioid analgesics; Opioid receptors; Pharmacology; Receptors; Receptors, Opioid, delta - chemistry; Receptors, Opioid, mu - chemistry; Rodents; Time Factors

Given the mounting evidence for involvement of δ opioid receptors in the tolerance and physical dependence of μ opioid receptor agonists, we have investigated the possible physical interaction between μ and δ opioid receptors by using bivalent ligands. Based on reports of suppression of antinocicept...