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Abstract
Fluoxetine (15 mg/kg i.p.) decreased the audiogenic seizure intensity in 33% of severe
seizure genetically epilepsy-prone rats (GEPR-9s). 5-Hydroxytryptophan (5-HTP, 12.5
mg/kg i.p.) produced no anticonvulsant effect in GEPR-9s. When GEPR-9s were treated
with a combination of these two drugs, the combination treatment decreased the audiogenic
seizure intensity in 83% of the animals tested. Brain microdialysis studies showed
that the same combination of 5-HTP and fluoxetine also produced a marked potentiation
of the increase in the extracellular serotonin concentration in the thalamus of freely-moving
GEPR-9s when compared with administration of either drug alone. A negative correlation
between audiogenic seizure intensity and extracellular serotonin concentration existed
after either fluoxetine alone or the combination treatment. No significant changes
in extracellular norepinephrine concentrations were observed after the combination
treatment. These results coupled with our earlier reports strongly suggest that a
serotonergic mechanism is involved in the anticonvulsant effects of fluoxetine in
GEPRs.