engleski

Acute and repeated fluoxetine treatment decrease the convulsant potency of picrotoxin in unstressed and stressed mice

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. Male CBA mice were prior to exposure to stress (10-min swimming at 18-19°C) and the i.v. infusion of picrotoxin (starting 15 min after termination of stress), pre-treated with fluoxetine either acutely (10 and 20 mg/kg i.p. 40 min prior to stress) or repeatedly (20 mg/kg once daily for 5 consecutive days) and the latency to the onset of two convulsant signs and death was registered. In accordance with our results published previously (Pericic et al., Psychopharmacology 158: 87-93, 2001), swim stress enhanced significantly the doses of picrotoxin needed to produce running bouncing (RB) clonus, tonic hindlimb extension (THE) and death. Fluoxetine (10 mg/kg) enhanced the dose of picrotoxin needed to produce tonic hindlimb extension (THE) in stressed but not in unstressed mice. A higher dose of this drug (20 mg/kg) increased the dose of picrotoxin producing THE and death in unstressed and swim stressed mice. Neither of this treatments affected running bouncing (RB) clonus. Repeated treatment with fluoxetine (20 mg/kg i.p.) exerted an even more pronounced anticonvulsant effect. This treatment significantly enhanced in unstressed and swim-stressed mice doses of picrotoxin needed to produce RB clonus, THE and death. 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, at least against convulsions produced by the blockade of GABAergic transmission. While swim stress attenuated the anticonvulsant property of acute fluoxetine, it failed to affect this property of repeated fluoxetine treatment.

fluoxetine; acute and chronic treatment; stress; convulsions; picrotoxin

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