title: Stimulus properties of fluvoxamine in a conditioned taste aversion procedure.
abstract: A conditioned taste aversion (CTA) procedure in mice was used to investigate the stimulus effects of the serotonin reuptake inhibitors (SSRIs) fluvoxamine and fluoxetine. Fluvoxamine elicited a reliable CTA (ED50 = 24 mg/kg, SC) and a number of drugs were tested as pre-exposure drugs. Pre-exposure to the serotonin (5-HT)1A receptor agonists flesinoxan and +/- -8-hydroxy-dipropylaminotetralin (8-OH-DPAT) prevented the CTA induced by fluvoxamine (50 mg/kg, SC). Pre-exposure with the 5-HT2C receptor agonist MK 212 [6-chloro-2(1-piperazinyl)pyrazine] partially prevented the fluvoxamine-induced CTA, pre-exposure with the 5-HT2A/2C receptor agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] did not prevent the CTA induced by fluvoxamine. Flesinoxan pre-exposure also prevented the taste aversion induced by fluoxetine (10 mg/kg, SC) completely. This contrasts previous results obtained with fluoxetine, where was found that its stimulus is primarily mediated by 5-HT2C, and to a lesser degree by 5-HT1A receptors. Therefore, we compared the two SSRIs directly. Pre-exposure to fluvoxamine prevented the fluoxetine-induced CTA, whereas pre-exposure to fluoxetine only partially prevented the fluvoxamine-induced CTA. We conclude that 5-HT1A receptors are involved in the stimulus properties of both fluvoxamine and fluoxetine, that 5-HT2C receptors are involved in fluvoxamine and especially fluoxetine, and, based primarily on the cross-comparison tests, that the two SSRIs have somewhat different stimulus properties.
authors.affiliation: Department of Psychopharmacology, Faculty of Pharmacy, Utrecht University, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Gommans
authors.forename: J A
authors.initials: JA
authors.lastname: Bouwknecht
authors.forename: T H
authors.initials: TH
authors.lastname: Hijzen
authors.forename: H H
authors.initials: HH
authors.lastname: Berendsen
authors.forename: C L
authors.initials: CL
authors.lastname: Broekkamp
authors.forename: R A
authors.initials: RA
authors.lastname: Maes
authors.forename: B
authors.initials: B
authors.lastname: Olivier
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013649:Taste / Q000187:drug effects*
chemical_list: D005473:Fluoxetine; D016666:Fluvoxamine; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors