Title:Subacute Fluoxetine Reduces Signs of Hippocampal Damage Induced by a Single Convulsant Dose of 4-Aminopyridine in Rats
Volume: 16
Issue: 6
Author(s): Ahmed A. Shiha, Rubén Fernández de la Rosa, Mercedes Delgado, Miguel A. Pozo and Luis García-García*
Affiliation:
- Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII nº 1, 28040 Madrid,Spain
Keywords:
4-aminopyridine, astrogliosis, brain metabolism, fluoxetine, hippocampus, positron emission tomography, selective
serotonin reuptake inhibitor, seizure.
Abstract: Background: Epilepsy is a central disorder associated with neuronal damage and brain hypometabolism.
It has been reported that antidepressant drugs show anticonvulsant and neuroprotective
effects in different animal models of seizures and epilepsy.
Aims: The purpose of this study was to investigate the eventual short-term brain impairment induced by a
single low convulsant dose of the potassium channel blocker 4-aminopyridine (4-AP) and the eventual
neuroprotective effects exerted by fluoxetine, a prototypical selective serotonin (5-hydroxytryptamine;
5-HT) reuptake inhibitor (SSRI).
Method:
In vivo 2-deoxy-2-[
18F]fluoro-D-glucose ([
18F]FDG) positron emission tomography (PET)
and several histological assessments were carried out in adult male rats after i.p. administration of 3
mg/kg 4-AP for evaluating eventual brain metabolism impairment and signs of hippocampal damage.
We also evaluated the effects of a short-term fluoxetine treatment (10 mg/kg, i.p. for 7 days) in this
seizure model.
Results: [
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 effects of fluoxetine, this SSRI showed beneficial neurologic
effects, since it significantly increased the seizure latency time and reduced the abovementioned
4-AP-induced hippocampal damage markers.
Conclusion: Overall, our results point to SSRIs and eventually endogenous 5-HT as neuroprotective
agents against convulsant-induced hippocampal damage.
