title: Antidepressant-like effects of paroxetine are produced by lower doses than those which produce nausea.
abstract: Paroxetine is prescribed to treat depression, but it also produces nausea. The potential of animal models to detect nauseating, antidepressant-like, and rewarding/aversive effects of paroxetine were assessed. In Experiments 1 (spaced conditioning trials) and 3 (massed conditioning trials), a dose of 30 mg/kg, but not lower doses (3 and 10 mg/kg) of paroxetine produced conditioned gaping reactions (reflective of nausea) in the Taste Reactivity (TR) test. In Experiment 2, when administered 23.5, 5 and 1 h prior to a 5 min forced swim test (FST) a dose as low as 3 mg/kg of paroxetine increased swimming and decreased immobility (reflective of antidepression) compared to controls. In Experiment 3, neither 10 nor 30 mg/kg of paroxetine produced a conditioned floor preference/aversion, but both doses decreased activity during conditioning trials. These results suggest that paroxetine produced an antidepressant-like effect at a lower dose (3 mg/kg) than that necessary to produce nausea (30 mg/kg). The TR test may be beneficial for assessing the side effect of nausea in preclinical tests of new compounds.
authors.affiliation: University of Guelph, Ontario, Canada.
authors.forename: Katharine J
authors.initials: KJ
authors.lastname: Tuerke
authors.forename: Francesco
authors.initials: F
authors.lastname: Leri
authors.forename: Linda A
authors.initials: LA
authors.lastname: Parker
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009325:Nausea / Q000139:chemically induced*; D017374:Paroxetine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D013550:Swimming / Q000523:psychology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine