title: Effect of repeated administration of U-50,488H, a kappa opioid receptor agonist, on central 5-HT1 and 5-HT2 receptors in the rat.
abstract: The effect of repeated administration of U-50,488H, a kappa-opioid receptor agonist, on the development of tolerance to its analgesic effect and on the 5-HT1 and 5-HT2 receptors in the cerebral cortex and spinal cord of the rat were determined. Male Sprague-Dawley rats were injected twice daily with U-50,488H, (25 mg/kg, i.p.) or its vehicle for 4 days. The assessment of tolerance to the analgesic effect and biochemical determinations were made on day 5. Repeated administration of U-50,488H resulted in the development of tolerance to its analgesic effect. The 5-HT1 and 5-HT2 receptors were characterized by using 3H-5-hydroxytryptamine (3H-5-HT) and 3H-spiperone as the ligands and unlabeled 5-hydroxytryptamine (5-HT) and ketanserin, respectively, to determine the nonspecific binding. In the spinal cord 3H-5-HT bound to 5-HT1 receptors at a single high-affinity site with a Bmax value of 41.3 +/- 9.6 fmol/mg protein and a Kd value of 22.6 +/- 7.0 nmol/l. 3H-Spiperone bound to 5-HT2 receptors in the spinal cord with a Bmax value of 16.1 +/- 3.8 fmol/mg protein and a Kd value of 0.36 +/- 0.15 nmol/l. Repeated administration of U-50,488H to rats did not affect spinal cord 5-HT1 and 5-HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacodynamics, University of Illinois, Chicago.
authors.forename: A
authors.initials: A
authors.lastname: Gulati
authors.forename: P
authors.initials: P
authors.lastname: Ramarao
authors.forename: H N
authors.initials: HN
authors.lastname: Bhargava
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000648:ultrastructure; D004361:Drug Tolerance; D008297:Male; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D013116:Spinal Cord / Q000648:ultrastructure
chemical_list: D000700:Analgesics; D011759:Pyrrolidines; D011985:Receptors, Serotonin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer