Long-term alteration in the central monoaminergic systems of the rat by 2,4,5-trihydroxyamphetamine but not by 2-hydroxy-4,5-methylenedioxymethamphetamine or 2-hydroxy-4,5-methylenedioxyamphetamine.
I Elayan, James W. Gibb, Glen R. Hanson, R L Foltz, H K Lim, M Johnson
European Journal of Pharmacology October 1, 1992 DOI: 10.1016/0014-2999(92)90714-f (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats (male Sprague-Dawley implied by field context; not stated in abstract) |
| Interventions | 2 4 5-trihydroxyamphetamine 6-OH-MDMA 6-OH-MDA |
| Dose | 0.25 and 0.5 micromol 2,4,5-trihydroxyamphetamine; 1 micromol 6-OH-MDMA; 1 micromol 6-OH-MDA |
| Duration | 7 days (2,4,5-trihydroxyamphetamine); 14 days (6-OH-MDMA and 6-OH-MDA) |
| Measures | Tryptophan hydroxylase (TPH) activity, tyrosine hydroxylase (TH) activity, norepinephrine (NE) concentration |
| Topics | Serotonin MDMA |
| Keywords | Brain Animals Rats, sprague-dawley Norepinephrine Dopamine Amphetamines N-methyl-3,4-methylenedioxyamphetamine Tryptophan hydroxylase Tyrosine 3-monooxygenase Male |
| Key findings | Intracerebroventricular 2,4,5-trihydroxyamphetamine, an MDMA metabolite, sharply reduced hippocampal tryptophan hydroxylase activity (to 5% and 1% of control at 0.25 and 0.5 micromoles) and norepinephrine levels, and lowered striatal and nigral tyrosine hydroxylase activity. The authors propose that formation of this metabolite may help explain how MDMA destroys serotonergic nerve terminals. |
Abstract
The long-term effects of three metabolites of 3,4-methylenedioxymethamphetamine (MDMA) on the central monoaminergic systems of the rat were examined. Seven days after the intracerebroventricular administration of 0.25 and 0.5 mumol 2,4,5-trihydroxyamphetamine, hippocampal tryptophan hydroxylase (TPH) activity was reduced to 5 and 1% of control, respectively, while norepinephrine (NE) concentration was depressed to 10 and 18% of control. These two respective dosages also decreased striatal tyrosine hydroxylase (TH) activity to 67 and 10% of control, respectively, while nigral TH activity was reduced to 59 and 20% of control. Striatal TPH activity was reduced to 74 and 81% of control, respectively, while the activity in the dorsal and median raphe remained unaltered. The intracerebroventricular administration of 1 mumol 2-hydroxy-4,5-methylenedioxymethamphetamine (6-OH-MDMA) failed to alter TPH activity, TH activity or NE concentration after 14 days. In contrast, 1 mumol of 2-hydroxy-4,5-methylenedioxyamphetamine (6-OH-MDA) induced a 30% increase in striatal TPH activity and a 50% increase in nigral TH activity. The study of the formation of 2,4,5-trihydroxyamphetamine after MDMA treatment may provide insight as to how MDMA destroys serotonergic nerve terminals.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- The Role of Metabolism in 3,4-(±)-Methylenedioxyamphetamine and 3,4-(±)-Methylenedioxymethamphetamine (Ecstasy) toxicity Therapeutic Drug Monitoring March 19, 2004
- Serotonergic Neurotoxicity of 3,4-(±)-Methylenedioxyamphetamine and 3,4-(±)-Methylendioxymethamphetamine (Ecstasy) Is Potentiated by Inhibition of γ-Glutamyl Transpeptidase Chemical Research in Toxicology May 31, 2001
- Further studies on the role of metabolites in (+/-)-3,4-methylenedioxymethamphetamine-induced serotonergic neurotoxicity. Drug Metabolism and Disposition October 2009
- Synthesis and cytotoxic profile of 3,4-methylenedioxymethamphetamine ("ecstasy") and its metabolites on undifferentiated PC12 cells: A putative structure-toxicity relationship. Chemical Research in Toxicology October 2006
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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. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- Effects of 3,4-dihydroxymethamphetamine and 2,4,5-trihydroxymethamphetamine, two metabolites of 3,4-methylenedioxymethamphetamine, on central serotonergic and dopaminergic systems. Journal of Pharmacology and Experimental Therapeutics May 1, 1992
- Synthesis and neurotoxicological evaluation of putative metabolites of the serotonergic neurotoxin 2-(methylamino)-1-[3,4-(methylenedioxy)phenyl] propane [(methylenedioxy)methamphetamine]. Chemical Research in Toxicology 1992
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