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Chronic administration of citalopram inhibited El mouse convulsions and decreased monoamine oxidase-A activity
Abstract:
Serotonin (5-HT) is thought to play an important role in the seizures of El mice because the seizure threshold of El mice correlates with the 5-HT concentration in the central nervous system. In this study, the anticonvulsant effect of a 5-HT reuptake blocker, citalopram, was evaluated behaviorally and biochemically. El mouse convulsions were inhibited by chronic administration of citalopram (80 mg/kg/day, p.o. for 2 weeks), but were not inhibited by acute administration of citalopram (80 mg/kg, i.p., 2 h after single injection). Both chronic and acute administration of citalopram decreased the concentration of 5-hydroxyindolacetic acid in the brain, whereas the concentration of 5-HT was not changed by treatment with citalopram. Tryptophan hydroxylase activity was not different between the citalopram and control groups, although the monoamine oxydase-A activity was lowered by chronic administration of citalopram. These findings suggest that both acute and chronic administration of citalopram depresses the 5-HT turnover rate, however chronic administration is necessary to inhibit El mouse convulsions.
Insights
Chronic administration of citalopram, a serotonin (5-HT) reuptake blocker, effectively inhibited seizures in El mice. This anticonvulsant effect required long-term treatment, unlike acute administration, suggesting a role for serotonin turnover in seizure control.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Serotonin (5-HT) is implicated in El mouse seizures, with seizure threshold correlating to central nervous system 5-HT levels.
- Selective serotonin reuptake inhibitors (SSRIs) are potential anticonvulsant agents.
Purpose of the Study:
- To evaluate the anticonvulsant effects of citalopram, a 5-HT reuptake blocker, in El mice.
- To investigate the biochemical mechanisms underlying citalopram's effects on serotonin metabolism.
Main Methods:
- Behavioral assessment of seizure inhibition in El mice following citalopram administration.
- Biochemical analysis of brain serotonin (5-HT) and its metabolites (5-HIAA).
- Enzyme activity assays for tryptophan hydroxylase and monoamine oxidase-A.
Main Results:
- Chronic citalopram administration (80 mg/kg/day for 2 weeks) inhibited El mouse convulsions.
- Acute citalopram administration did not inhibit convulsions.
- Both chronic and acute citalopram decreased 5-hydroxyindoleacetic acid (5-HIAA) levels, indicating reduced 5-HT turnover.
- Chronic citalopram lowered monoamine oxidase-A activity.
Conclusions:
- Chronic administration of citalopram is necessary for its anticonvulsant effect in El mice.
- Citalopram depresses serotonin turnover, with chronic treatment being crucial for seizure inhibition.
- The findings highlight the importance of sustained SSRI treatment for managing certain seizure types.