engleski

Effects of selective serotonin reuptake inhibitor fluoxetine under the condititions of stress

Introduction: Serotonin reuptake inhibitors (SSRI) are the most widely used antidepressant drugs while fluoxetine is the third most prescribed. Fluoxetine is used for the treatment of major depression (including pediatric depression), obsessive-compulsive disorder (in both adult and pediatric populations), bulimia nervosa, panic disorder and premenstrual dysphoric disorder. Since depression and epilepsy often appear in the same patient it is important to asses wheather drugs used in depression have pro- or anticonvulsant properties as well as could their action be modified by stress. The aim of this study was to assess whether fluoxetine, a well known antidepressant drug and 5-HT reuptake inhibitor, affects the seizure threshold in unstressed and/or stressed mice. Methods: In our exprements we used biological stress (acute swimm stress) with predictive value for antidepressant drugs. Namely, male CBA mice were, prior to exposure to stress, acutely (10 and 20 mg/kg) or repeatedly (20 mg/kg once daily for 5 consecutive days) pre-treated with fluoxetine and the latency to the onset of two convulsant signs and death was registered. Results: Lower dose of fluoxetine enhanced the dose of chemoconvulsant picrotoxine, non-competitive GABAA receptor antagonist, needed to produce tonic hind limb extension (THE) in stressed but not in unstressed mice, while the higher dose increased the dose of picrotoxin producing THE and death in unstressed as well as swim stressed mice. Running bouncing (RB) clonus was not affected. Repeated treatment with fluoxetine exerted an even more pronounced anticonvulsant effect. Namely, the dose of picrotoxine needed to produce convulsive signs in unstressed and swim-stressed mice. The results demonstrate that acute fluoxetine treatment had a greater anticonvulsant effect in unstressed than in stressed animals. On the other hand, repeated fluoxetine treatment had a similar anticonvulsant activity in stressed and unstressed animals. Conclusion: Fluoxetine (acute and repeated) showed anticonvulsant properties and this effect was present in unstressed and swim-stressed mice. The results also showed a pronounced anticonvulsant effect of swim stress against convulsions induced by GABA-related convulsants.

stress; fluoxetine; anticonvulsive effect

nije evidentirano