Synergistic interaction between ketoconazole and several antidepressant drugs with allopregnanolone treatments in ovariectomized Wistar rats forced to swim.
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.
Molina-Hernández
Miguel
M
Laboratorio de Conducta, Instituto de Investigaciones Psicológicas, Universidad Veracruzana, POB 361, Xalapa, Veracruz 91000, México. mimoli@todito.com
Tellez-Alcántara
Norma Patricia
NP
García
Julían Pérez
JP
Lopez
Jorge Ivan Olivera
JI
Jaramillo
M Teresa
MT
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
D000777:Anesthetics; D000928:Antidepressive Agents; D011280:Pregnanolone; D007654:Ketoconazole