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Dextromethorphan modulates the AP-1 DNA-binding activity induced by kainic acid
1Section of Pharmacology and Toxicology, Department of Pharmacy, College of Pharmacy, Kangwon National University, Korea Institute of Drug Abuse, Chunchon 200-701, South Korea.kimhc@cc.kangwon.ac.kr
Brain Research
|March 30, 1999
Summary
Dextromethorphan reduces kainic acid-induced neurotoxicity in rat hippocampus CA1 regions. This neuroprotection involves modulating activator protein-1 DNA-binding activity and Fos-related antigen expression.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Kainic acid induces neurotoxicity, particularly in the hippocampus.
- Dextromethorphan has shown dose-related neuroprotective effects.
Purpose of the Study:
- To investigate the neuroprotective mechanisms of dextromethorphan against kainic acid-induced neurotoxicity.
- To identify the specific hippocampal regions involved in dextromethorphan's effects.
Main Methods:
- Rats were pretreated with dextromethorphan before kainic acid administration.
- Activator protein-1 DNA-binding activity and Fos-related antigen expression were measured in hippocampal tissue.
- Specific regions analyzed included CA1, CA3, and the dentate gyrus.
Main Results:
- Dextromethorphan pretreatment significantly reduced kainic acid-induced activator protein-1 DNA-binding activity and Fos-related antigen expression in the CA1 region.
- These effects were not observed in the CA3 or dentate gyrus regions.
- Dextromethorphan alone elevated activator protein-1 DNA-binding activity and Fos-related antigen expression in the CA1 region for at least 4 days.
Conclusions:
- The CA1 area of the hippocampus is critical for mediating the neuroprotective effects of dextromethorphan.
- Dextromethorphan's interaction with activator protein-1 and Fos-related antigen pathways in CA1 may underlie its neuroprotective action.