Dextromethorphan blocks opioid peptide gene expression in the rat hippocampus induced by kainic acid

Neuropeptides
H C KimJ S Hong

Abstract

We have previously shown that dextromethorphan (DM) antagonizes kainic acid (KA)-induced neurotoxicity. Accumulating evidence indicates that the induction of seizure activity causes profound alterations in the levels of hippocampal opioid peptide mRNA. The present study was performed to further explore the effect of DM on KA-induced seizures as measured by hippocampal opioid peptide mRNA levels. Both Northern blot and in situ hybridization methods were used to examine the proenkephalin (PENK) and prodynorphin (PDYN) mRNA levels in the rat hippocampus. The robust seizure activity induced by KA correlated with a significant increase in hippocampal opioid peptide mRNA levels. Pretreatment of rats with DM decreased hippocampal PENK and PDYN mRNA levels and seizure activity induced by KA. Hippocampal PDYN mRNA levels fell quickly but PENK mRNA levels fell rather slowly, indicating that the PENK and PDYN mRNAs are differentially regulated. Our results demonstrate that DM modulates opioid peptide gene expression induced by KA, and that DM protects against KA-induced seizures.

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Citations

Aug 1, 1997·Archives of Pharmacal Research·K J JangH C Kim
Nov 6, 2010·Archives of Pharmacal Research·Eun-Joo ShinHyoung-Chun Kim
Apr 16, 2004·Behavioural Brain Research·Eun-Joo ShinHyoung-Chun Kim
Jun 27, 2001·Bioorganic & Medicinal Chemistry Letters·H C KimP H Lee
Jul 2, 2008·Chemical & Pharmaceutical Bulletin·Jong Yup KimJinhwa Lee
Jan 31, 2016·Pharmacology & Therapeutics·Linda NguyenRae R Matsumoto
May 25, 2011·Journal of Pharmacological Sciences·Eun-Joo ShinHyoung-Chun Kim
Dec 30, 2008·Plant Molecular Biology·Charles Q CaiJoseph F Petolino
Aug 2, 2003·Nature Reviews. Cancer·Sergio A Lamprecht, Martin Lipkin

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