title: Synergistic interaction between ketoconazole and several antidepressant drugs with allopregnanolone treatments in ovariectomized Wistar rats forced to swim.
abstract: This article was aimed to investigate the interest of the combination allopregnanolone plus ketoconazole in depression with the time-sampling method in the forced swimming task. Dose-response curves for fluoxetine (0.5, 1.0 or 2.0 mg/kg, twice day, during 2 weeks; i.p.), desipramine (0.5, 1.0 or 2.14 mg/kg, twice a day, during 2 weeks; i.p.), ketoconazole (6.25, 12.5, 25.0 and 37.5 mg/kg, once a day, during 2 weeks; i.p.) and allopregnanolone (0.5, 1.5, 2.0 mg/kg; once a day, during 2 weeks; s.c.) were established. Fluoxetine (1.0 mg/kg, p < 0.05; 2.0 mg/kg, p < 0.05) or ketoconazole (25.0 mg/kg, p < 0.05; 37.5 mg/kg, p < 0.05) produced antidepressant-like behavioral changes in swimming, highlighting a serotonergic mechanism while desipramine (1.0 mg/kg, p < 0.05; 2.14 mg/kg, p < 0.05) or allopregnanolone (1.5 mg/kg, p < 0.05; 2.0 mg/kg, p < 0.05) increased climbing behavior highlighting noradrenergic or dopaminergic effects. Subthreshold doses of fluoxetine (p < 0.05), desipramine (p < 0.05) or ketoconazole (p < 0.05) synergized with subthreshold doses of allopregnanolone and reduced immobility by increasing climbing. In conclusion, fluoxetine, desipramine, ketoconazole and allopregnanolone produced differential antidepressant-like actions in ovariectomized rats forced to swim. Ketoconazole, fluoxetine or desipramine synergized with allopregnanolone.
authors.affiliation: Laboratorio de Conducta, Instituto de Investigaciones Psicológicas, Universidad Veracruzana, POB 361, Xalapa, Veracruz 91000, México. mimoli@todito.com
authors.forename: Miguel
authors.initials: M
authors.lastname: Molina-Hernández
authors.forename: Norma Patricia
authors.initials: NP
authors.lastname: Tellez-Alcántara
authors.forename: Julían Pérez
authors.initials: JP
authors.lastname: García
authors.forename: Jorge Ivan Olivera
authors.initials: JI
authors.lastname: Lopez
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Jaramillo
mesh_terms: D000704:Analysis of Variance; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects*; D007398:Interpersonal Relations; D007654:Ketoconazole / Q000494:pharmacology*; D010052:Ovariectomy / Q000379:methods; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D013550:Swimming; D013997:Time Factors
chemical_list: D000777:Anesthetics; D000928:Antidepressive Agents; D011280:Pregnanolone; D007654:Ketoconazole