Subacute Fluoxetine Reduces Signs of Hippocampal Damage Induced by a Single Convulsant Dose of 4-Aminopyridine in Rats.

The purpose of this study was to investigate the eventual short-term brain impairment induced by a single convulsant dose of the potassium channel blocker 4-aminopyridine (4-AP). To this aim, in vivo 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) and several histological assessments were carried out after i.p. administration of 3 mg/kg 4-AP for evaluating eventual brain metabolism impairment and signs of hippocampal damage. On the other hand, it has been reported that antidepressant drugs show anticonvulsant and neuroprotective effects in different animal models of seizures and epilepsy. Therefore, we also evaluated the effects of a subacute treatment of the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) fluoxetine (10 mg/kg, i.p. for 7 days). [18F]FDG PET analysis revealed no changes in the regional brain metabolism on day 3 after 4-AP injection. The histological assessments revealed signs of damage in the hippocampus, a brain area usually affected by seizures. Thus, reactive gliosis and a significant increase in the expression of caspase-9 were found in the aforementioned brain area. By contrast, we observed no signs of neurodegeneration or neuronal death. Regarding the treatment with the antidepressant, subacute fluoxetine showed beneficial neurologic effects, since it significantly increased the seizure latency time and reduced the above-mentioned 4-AP-induced hippocampal damage markers. Overall, our results point to SSRIs and eventually endogenous 5-HT as neuroprotective agents against convulsant-induced hippocampal damage.