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PubMed · 1374469

Effect of flunarizine and nimodipine on the decrease in tryptophan hydroxylase activity induced by methamphetamine and 3,4-methylenedioxymethamphetamine.

M Johnson·K Mitros·D M Stone·R Zobrist·G R Hanson·J W Gibb
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Abstract

The effect of calcium channel blockers on the decrease in central tryptophan hydroxylase (TPH) activity and serotonin (5-HT) concentration induced by repeated large doses of methamphetamine (METH) or 3,4-methylenedioxymethamphetamine (MDMA) was evaluated. Rats received four or five injections of METH (10 or 15 mg/kg) or MDMA (10 mg/kg) at 6-h intervals, and were sacrificed 18 to 20 h or 1 week after the last administration. Flunarizine (30 mg/kg) prevented the decline in cortical and neostriatal TPH activity induced by MDMA, but failed to alter the effect of METH. The effect of flunarizine on the METH- and MDMA-induced changes in cortical 5-HT and 5-hydroxyindoleacetic acid concentrations paralleled the changes in enzyme activity. Nimodipine, diltiazem or TA-3090 failed to prevent the MDMA- and the METH-induced decline in TPH activity or in 5-HT and 5-hydroxyindoleacetic acid content. Because haloperidol failed to mimic the protective action of flunarizine, it is unlikely that flunarizine exerts its action by blocking the dopamine D-2 receptors. This study suggests that calcium influx may participate in the MDMA-induced decline in central TPH activity, and that the mechanism by which MDMA and METH decreases TPH activity differs.

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3,4-MethylenedioxyamphetamineAnimalsBrainChromatography, High Pressure LiquidDiltiazemDrug InteractionsEnzyme InductionFlunarizineHydroxyindoleacetic AcidInjections, SubcutaneousMaleMethamphetamineN-Methyl-3,4-methylenedioxyamphetamineNimodipineRatsRats, Inbred StrainsReceptors, DopamineReceptors, Dopamine D2SerotoninTryptophan HydroxylaseJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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M Johnson, K Mitros, D M Stone, R Zobrist, G R Hanson, J W Gibb. 1992. Effect of flunarizine and nimodipine on the decrease in tryptophan hydroxylase activity induced by methamphetamine and 3,4-methylenedioxymethamphetamine.. https://pubmed.ncbi.nlm.nih.gov/1374469/

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