Dextromethorphan modulates the AP-1 DNA-binding activity induced by kainic acid.
We have recently reported that dextromethorphan attenuates the neurotoxicity induced by kainic acid in a dose-related fashion. Pretreatments with dextromethorphan (50 mg/kg, p.o. x2) significantly reduced the activator protein-1 DNA-binding activity and the Fos-related antigen-immunoreactive protein induced by kainic acid (10 mg/kg, i.p.) in the CA1, but not the CA3 or the dentate gyrus sector of the rat hippocampus. Paradoxically, dextromethorphan itself caused an elevated activator protein-1 DNA-binding activity and Fos-related antigen-immunoreactive protein in the CA1 region which lasted for at least 4 days. The results suggest that the CA1 area is the critical site for mediating the putative neuroprotective effect induced by dextromethorphan.
Kim
H C
HC
Section 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
Bing
G
G
Jhoo
W K
WK
Ko
K H
KH
Kim
W K
WK
Lee
D C
DC
Shin
E J
EJ
Hong
J S
JS
D000818:Animals; D004247:DNA / Q000378:metabolism*; D003915:Dextromethorphan / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D003915:Dextromethorphan; D004247:DNA; D007608:Kainic Acid