title: Sex and age differences in the antidepressant-like effect of fluoxetine in the forced swim test.
abstract: This study compared in males and females of three representative ages: young adults (3-5months old), middle-aged (12-15months old) and senescent (23-25months old) the antidepressant-like effect of fluoxetine (FLX, 5.0 and 10mg/kg) in the forced swim test (FST). Intact (non gonadectomized) rats were evaluated. Young adult females were chosen in proestrus/estrus or in metestrus/diestrus, while middle-aged and senescent females were selected in metestrus/diestrus. Locomotion and motor coordination were also recorded. Under basal conditions (without FLX), young adult and middle-aged females showed less immobility than males. This sex difference disappeared at senescence because males diminished their levels of immobility. Thus, senescent males showed lower immobility than middle-aged and young males. FLX (5 and 10mg/kg) produced similar actions in young females irrespective of their estrous cycle phase, therefore, these subgroups were pooled in a single one. Young adult and middle aged females clearly responded to 5 and 10mg/kg of FLX with a reduction in immobility, while young adult and middle-aged males only did to 10mg/kg. In senescent females 10mg/kg FLX reduced immobility. Remarkably, in senescent males this FLX dose did not produce an antidepressant-like effect. FLX marginally affected locomotion; however, at its highest dose (10mg/kg), and only in senescent males, interfered with motor coordination tested in the rotarod. These data show that sex and aging influence behavioral despair without treatment and after FLX.
authors.affiliation: Departamento de Farmacobiología, Cinvestav, México D.F., México. Electronic address: jfernand@cinvestav.mx.
authors.forename: Alonso
authors.initials: A
authors.lastname: Fernández-Guasti
authors.affiliation: Departamento de Farmacobiología, Cinvestav, México D.F., México; Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", México D.F., México.
authors.forename: Maribel
authors.initials: M
authors.lastname: Olivares-Nazario
authors.affiliation: Departamento de Farmacobiología, Cinvestav, México D.F., México.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Reyes
authors.affiliation: Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", México D.F., México.
authors.forename: Lucía
authors.initials: L
authors.lastname: Martínez-Mota
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D030762:Estrous Cycle; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D046353:Immobility Response, Tonic / Q000187:drug effects*; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D051381:Rats; D012727:Sex Characteristics; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine
keywords: Depressive-like behavior; Fluoxetine; Forced swim test; Sex and age differences