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Wednesday 01 December 2004

Synergistic interaction between ketoconazole and several antidepressant drugs with allopregnanolone treatments in ovariectomized Wistar rats forced to swim.

By: Molina-Hernandez M, Tellez-Alcantara NP, Garcia JP, Lopez JI, Jaramillo MT.

Prog Neuropsychopharmacol Biol Psychiatry 2004 Dec;28(8):1337-45

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.

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