Role of serotonin in the anticonvulsant effect of fluoxetine in genetically epilepsy-prone rats.
This study was designed to demonstrate a role of serotonin in the anticonvulsant effect of fluoxetine, a serotonin reuptake inhibitor, in genetically epilepsy-prone rats. When varied doses of 5-hydroxytryptophan (12.5, 25, 50 mg/kg) were administered i.p. along with a fixed dose of fluoxetine (15 mg/kg) to severe seizure genetically epilepsy-prone rats, the severity of audiogenic seizures was decreased dose-dependently, and the combination treatment also produced a marked potentiation of the anticonvulsant effect when compared with administration of either drug alone. Pretreatment of severe seizure genetically epilepsy-prone rats with p-chlorophenylalanine depleted brain serotonin and reduced the anticonvulsant effectiveness of fluoxetine. By using intracerebral microdialysis, the depletion of serotonin after p-chlorophenylalanine treatment was confirmed by measuring thalamic extracellular serotonin and 5-hydroxyindoleacetic acid concentrations during basal release and in response to a challenge dose of fluoxetine. We concluded that serotonergic transmission may be involved in the anticonvulsant effect of fluoxetine in severe seizure genetically epilepsy-prone rats.
Yan
Q S
QS
Department of Basic Sciences, University of Illinois College of Medicine at Peoria 61656.
Jobe
P C
PC
Cheong
J H
JH
Ko
K H
KH
Dailey
J W
JW
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D051381:Rats; D012701:Serotonin / Q000032:analysis / Q000502:physiology*; D013788:Thalamus / Q000737:chemistry
D000927:Anticonvulsants; D005473:Fluoxetine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D010134:Fenclonine