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, Glen R. Hanson, James W. Gibb
Journal of Pharmacology and Experimental Therapeutics May 1, 1992 DOI: 10.1016/s0022-3565(25)11079-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats (male, inbred strains) given repeated doses of methamphetamine or MDMA |
| Interventions | Methamphetamine MDMA Flunarizine Nimodipine Diltiazem TA-3090 Haloperidol |
| Dose | METH 10 or 15 mg/kg; MDMA 10 mg/kg; flunarizine 30 mg/kg |
| Duration | Four or five injections at 6-h intervals; sacrificed 18 to 20 h or 1 week after the last administration |
| Topics | Serotonin MDMA |
| Keywords | Brain Animals Rats, inbred strains Methamphetamine N-methyl-3,4-methylenedioxyamphetamine Hydroxyindoleacetic acid Flunarizine Nimodipine Diltiazem Tryptophan hydroxylase Receptors, dopamine d2 Injections, subcutaneous Enzyme induction Drug interactions Male |
| Key findings | Flunarizine (30 mg/kg) prevented the MDMA-induced decline in cortical and neostriatal tryptophan hydroxylase activity and the parallel changes in cortical serotonin and 5-hydroxyindoleacetic acid, but did not alter methamphetamine's effects. Nimodipine, diltiazem, and TA-3090 did not prevent declines from either drug, and haloperidol did not mimic flunarizine. The authors suggest calcium influx may participate in MDMA-induced TPH decline and that MDMA and METH lower TPH activity by different mechanisms. |
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.
Comparable studies
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| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
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| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 8
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Studies on the mechanisms underlying amiloride enhancement of 3,4-methylenedioxymethamphetamine-induced serotonin depletion in rats. European Journal of Pharmacology May 21, 2007
- Neuroadaptive Changes in 5-HT1A Autoreceptor Sensitivity Following High-Dose MDMA Treatment 2011
- Acute concomitant effects of MDMA binge dosing on extracellular 5-HT, locomotion and body temperature and the long-term effect on novel object discrimination in rats. Psychopharmacology July 20, 2010
- Population pharmacokinetics of 3,4-methylenedioxymethamphetamine and main metabolites in rats. Toxicological sciences : an official journal of the Society of Toxicology March 2010
and 3 more in the library