title: Serotonin involvement in the discriminative stimulus effects of kappa opioids in pigeons.
abstract: The purpose of the present study was to examine the role of serotonin (5HT) in the discriminative stimulus effects of kappa opioids. Pigeons were trained to discriminate 5.6 mg/kg of the kappa opioid, U50,488, from water. During substitution tests, both U50,488 and another kappa opioid, spiradoline, produced > 80% responding on the U50,488-appropriate key. In contrast, the non-opioid compound, phencyclidine and several serotonergic compounds failed to substitute for the U50,488 discriminative stimulus across a wide range of doses. During combination tests, the selective 5HT1A agonist, 8-OH-DPAT (0.001-3.2 mg/kg), dose-dependently attenuated the discriminative stimulus effects of 5.6 mg/kg U50,488 and 3.2 mg/kg spiradoline. This effect was reversed by the 5HT1A antagonist, NAN-190 (0.01-1 mg/kg), in a dose-dependent manner. Buspirone (0.01-10 mg/kg), a 5HT1A partial agonist, also attenuated the discriminative stimulus effects of the training dose of U50,488 but ipsapirone, another 5HT1A partial agonist, did not. Ketanserin, a 5HT2 antagonist, and MDL72222, a 5HT3 antagonist, attenuated the effects of U50,488, whereas the 5HT1B,1C agonist, mCPP, and the 5HT2 agonist, DOI, did not. Depletion of 5HT with p-CPA also attenuated U50,488's discriminative stimulus effects. Taken together, the results suggest that serotonin release is an important component in the discriminative stimulus effects produced by kappa opioids; however, the effects of DOI and mCPP alone suggest that activation of post-synaptic 5HT receptors is not sufficient to produce the full spectrum of kappa opioid discriminative stimulus effects.
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill.
authors.forename: M E
authors.initials: ME
authors.lastname: Bronson
authors.forename: Y P
authors.initials: YP
authors.lastname: Lin
authors.forename: K
authors.initials: K
authors.lastname: Burchett
authors.forename: M J
authors.initials: MJ
authors.lastname: Picker
authors.forename: L A
authors.initials: LA
authors.lastname: Dykstra
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D010856:Columbidae; D003216:Conditioning, Operant / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D000700:Analgesics; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D010134:Fenclonine