5-HT2 receptor-mediated potentiation of dopamine synthesis and central serotonergic deficits.
European Journal of Pharmacology July 1, 1993 DOI: 10.1016/0014-2999(93)90859-g (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats (Sprague-Dawley), striatal tissue |
| Interventions | R-DOI MMAI Amphetamine MDMA NSD-1015 |
| Duration | Rats killed 45 min after first injection; binding assessed one week after killing |
| Measures | Striatal DOPA accumulation, [3H]paroxetine binding |
| Topics | Serotonin |
| Keywords | Hippocampus Corpus striatum Animals Rats, sprague-dawley Dopamine Dihydroxyphenylalanine Amphetamines N-methyl-3,4-methylenedioxyamphetamine Hydrazines Indans Receptors, serotonin Serotonin antagonists Male Serotonin receptor agonists |
| Key findings | R-DOI, MMAI, or amphetamine given alone did not increase striatal DOPA accumulation, but amphetamine combined with either MMAI or R-DOI significantly increased it. Multiple doses of the R-DOI and amphetamine combination did not decrease [3H]paroxetine binding sites at one week. The authors conclude that MDMA's dopamine-synthesis-increasing effect depends on both 5-HT2 receptor stimulation and dopamine efflux. |
Abstract
The hypothesis was tested that serotonin (5-HT) modulates 3,4-methylenedioxymethamphetamine (MDMA)-induced increase in dopamine synthesis. Rats were treated with the selective 5-HT2 receptor agonist (R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (R-DOI), the selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan (MMAI), amphetamine, MDMA, or a combination of amphetamine and R-DOI or MMAI, followed by the L-dihydroxyphenylalanine (DOPA) decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD-1015). Rats were killed 45 min after the first injection and striatal DOPA was determined. R-DOI, MMAI, or amphetamine alone did not increase DOPA accumulation. However, combination of amphetamine with either MMAI or R-DOI significantly increased DOPA accumulation. Multiple doses of the R-DOI and amphetamine combination did not decrease [3H]paroxetine binding sites at one week after killing. The results indicate that the dopamine synthesis increasing effect of MDMA depends both on 5-HT2 receptor stimulation and dopamine efflux.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
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|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 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 6
- Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists. European Journal of Pharmacology November 3, 1994
- The abused drug MDMA (Ecstasy) induces programmed death of human serotonergic cells The FASEB Journal February 1, 1997
- Hallucinogens. Pharmacology & Therapeutics February 1, 2004
- On the Mechanisms Underlying 3,4-Methylenedioxymethamphetamine Toxicity: The Dilemma of the Chicken and the Egg Neuropsychobiology 2009
- Risperidone attenuates and reverses hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats. Neurotoxicology November 2008
and 1 more in the library
Cites 16
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- 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
- Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class Journal of Medicinal Chemistry October 1, 1986
- 5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine European Journal of Pharmacology November 1, 1992
- Nonneurotoxic tetralin and indan analogs of 3,4-(methylenedioxy)amphetamine (MDA) Journal of Medicinal Chemistry February 1, 1990
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