Cross-tolerance to acute administration of mu and kappa opioid agonists at the spinal cord level in the rat.
Development of tolerance and cross-tolerance after acute administration of the mu agonist morphine and the kappa agonist U-50,488H was assessed in rats, through recording of a C-fiber-evoked spinal nociceptive reflex. Rats rendered tolerant to morphine (a single dose of 1 mg/kg i.p.) showed, after a 5-hour period, tolerance to morphine and cross-tolerance to the kappa-opioid receptor agonist U-50,488H, as revealed by depressed C-reflex responsiveness. In contrast, pretreatment with U-50,488H (a single dose of 1 mg/kg i.p.) rendered tolerant the rats to U-50,488H, but the animals did not develop cross-tolerance to morphine. Results indicate that acute administration of mu and kappa ligands leads to development of unidirectional cross-tolerance in rat spinal cord. This points to limitations in using alternated mu and kappa opioid agonists to bypass the problem of development of opioid tolerance in chronic pain complaints.
Laurido
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C
Department of Biological Sciences, Faculty of Chemistry and Biology, University of Santiago of Chile, Chile.
Hernandez
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A
Perez
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H
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004361:Drug Tolerance; D006614:Hindlimb / Q000294:innervation; D007274:Injections, Intraperitoneal; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology
D000700:Analgesics; D000701:Analgesics, Opioid; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine