title: Discriminative stimulus properties of eltoprazine in the pigeon.
abstract: Twelve pigeons were successfully (ED50 = 2.4 mg/kg p.o.) trained to discriminate the 5-HT(1A/B) receptor agonist eltoprazine (5.0 mg/kg p.o.) from its vehicle in a fixed-ratio (FR)30 two-key operant drug discrimination procedure. Tests for generalization and antagonism showed that 5-HT1A receptor agonists, such as 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) (66.7%), flesinoxan (72.7%), buspirone (58.3%), and ipsapirone (36.4%) only partially substituted for the eltoprazine cue. Compounds with mixed agonistic action at 5-HT1 receptors, completely (> or = 80%) [(eltoprazine; TFMPP (1-(3-trifluoromethylphenyl) piperazine (ED50 = 7.68 mg/kg) and RU 24969 (5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl-1H-indole) (ED50 = 15.8 mg/kg)] substituted for eltoprazine; whereas m-CPP (1-(3-chlorophenyl)piperazine) did not. The selective 5-HT reuptake inhibitor fluvoxamine partially (44%) substituted for the eltoprazine cue. The 5-HT1A receptor antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phtalimido)butyl]piperazine) fully blocked the eltoprazine cue. Both (+/-)-pindolol and (+/-)-propranolol showed partial antagonism of the eltoprazine cue (66.7 and 50.0%, respectively). (+/-)-Pindolol also showed partial substitution (50%) for the eltoprazine cue, but NAN-190 and (+/-)propranolol did not. It is concluded that the discriminatory stimulus properties of eltoprazine in the pigeon are mediated by 5-HT1A and 5-HT1B receptors.
authors.affiliation: CNS-Pharmacology, Solvay Pharmaceuticals B.V., Weesp, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Olivier
authors.forename: A
authors.initials: A
authors.lastname: Herremans
authors.forename: J
authors.initials: J
authors.lastname: Mos
authors.forename: M
authors.initials: M
authors.lastname: van Drimmelen
authors.forename: M
authors.initials: M
authors.lastname: Tulp
authors.forename: R
authors.initials: R
authors.lastname: van Oorschot
authors.forename: T
authors.initials: T
authors.lastname: Hijzen
mesh_terms: D000818:Animals; D010856:Columbidae; D003216:Conditioning, Operant / Q000187:drug effects; D004193:Discrimination Learning; D004192:Discrimination, Psychological / Q000187:drug effects*; D005795:Generalization, Stimulus / Q000187:drug effects; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D012055:Reinforcement Schedule; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; C063828:eltoprazine