Anticonvulsant doses of carbamazepine increase hippocampal extracellular serotonin in genetically epilepsy-prone rats: dose response relationships

The antiepileptic drug carbamazepine produces dose related anticonvulsant effects in genetically epilepsy-prone rats (GEPRs) and most other animal seizure models. Carbamazepine releases serotonin as part of the pharmacodynamic action by which it suppresses convulsions in GEPRs and it releases seroto...

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Bibliographic Details
Published in:Neuroscience letters 1997-05, Vol.227 (1), p.13-16
Main Authors: Dailey, John W, Reith, Maarten E.A, Yan, Qing-Shan, Li, Ming-Ya, Jobe, Phillip C
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Anticonvulsants - pharmacology
Anticonvulsants. Antiepileptics. Antiparkinson agents
Antiepileptic drug
Biological and medical sciences
Carbamazepine
Carbamazepine - pharmacology
Convulsions
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Epilepsy - drug therapy
Epilepsy - genetics
Epilepsy - metabolism
Genetic Predisposition to Disease
Genetically epilepsy-prone rats
Hippocampus
Hippocampus - drug effects
Hippocampus - metabolism
Medical sciences
Microdialysis
Neuropharmacology
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Seizures
Serotonin
Serotonin - metabolism
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Summary:The antiepileptic drug carbamazepine produces dose related anticonvulsant effects in genetically epilepsy-prone rats (GEPRs) and most other animal seizure models. Carbamazepine releases serotonin as part of the pharmacodynamic action by which it suppresses convulsions in GEPRs and it releases serotonin in non-epileptic Sprague–Dawley rats. The two strains which make up the GEPR seizure model (moderate seizure GEPR-3s and severe seizure GEPR-9s) experience anticonvulsant effects in response to different doses of carbamazepine (GEPR-3 ED 50=25 mg/kg; GEPR-9 ED 50=3 mg/kg). The present study determined that carbamazepine produces a dose related increase in extracellular serotonin in each of the two GEPR strains. The doses of carbamazepine required to increase extracellular serotonin are similar to the doses required for an anticonvulsant effect in each of the strains. This result provides further support for the hypothesis that release of serotonin by carbamazepine is an important part of the pharmacodynamic action by which this drug suppresses seizures.
ISSN:0304-3940
1872-7972
DOI:10.1016/S0304-3940(97)00288-7