A PET study of effects of chronic 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) on serotonin markers in Göttingen minipig brain
Paul Cumming, Mette Møller, Kjeld Benda, Luciano Minuzzi, Steen Jakobsen, Svend Borup Jensen, Bente Pakkenberg, Anette Kirstine Stark, Jan Bert Gramsbergen, Mette Findal Andreasen, Aage Kristian Olsen Alstrup
Synapse April 5, 2007 DOI: 10.1002/syn.20377 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study with baseline and post-treatment PET imaging Peer reviewed |
|---|---|
| Population | Göttingen minipigs |
| Intervention | MDMA |
| Dose | greater than 20 mg/kg total; mean 42 mg/kg total |
| Duration | 2–4 days treatment, 2 weeks post-treatment imaging |
| Topics | MDMA Serotonin |
| Keywords | Neurochemical Serotonin transporter 5-HT Receptor Endocrinology Pharmacology |
| Citations | 28 |
| Key findings | MDMA doses above 20 mg/kg reduce serotonin transporter binding in the porcine brain without altering 5HT1A receptor binding or the number of serotonin neurons in the dorsal raphé nucleus. |
Abstract
Abstract The psychostimulant 3,4‐methylendioxymethamphetamine (MDMA, “ecstasy”) evokes degeneration of telencephalic serotonin innervations in rodents, nonhuman primates, and human recreational drug users. However, there has been no alternative to nonhuman primates for studies of the cognitive and neurochemical consequences of serotonin depletion in a large‐bodied animal. Therefore, we used positron emission tomography (PET) with [ 11 C]DASB to map the distribution of plasma membrane serotonin transporters in brain of Göttingen minipigs, first in a baseline condition, and again at 2 weeks after treatment with MDMA (i.m.), administered at a range of doses. In parallel PET studies, [ 11 C]WAY‐100635 was used to map the distribution of serotonin 5HT 1A receptors. The acute MDMA treatment in awake pigs evoked 1°C of hyperthermia. MDMA at total doses greater than 20 mg/kg administered over 2–4 days reduced the binding potential (pB) of [ 11 C]DASB for serotonin transporters in porcine brain. A mean total dose of 42 mg/kg MDMA in four animals evoked a mean 32% decrease in [ 11 C]DASB pB in mesencephalon and diencephalon, and a mean 53% decrease in telencephalic structures. However, this depletion of serotonin innervations was not associated with consistent alterations in the binding of [ 11 C]WAY‐100635 to serotonin 5HT 1A receptors. Stereological cell counting of serotonin‐positive neurons, which numbered 95,000 in the dorsal raphé nucleus of normal animals, was unaffected in MDMA‐treated group. group. Synapse 61:478–487, 2007. © 2007 Wiley‐Liss, Inc.
Comparable studies
Other experimental studies on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| Oxytocin-dependent reopening of a social reward learning critical period with MDMA | 2019 | Experimental study | |
| Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Rat whole brain synaptosomes | 1982 | Experimental study |
Citations in the library
Cited by 4
- In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin2A Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”) and Hallucinogen Users Archives of General Psychiatry June 6, 2011
- Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[¹⁸F]-ADAM/small-animal PET study. European Neuropsychopharmacology January 2016
- Measuring effects of MDMA (ecstasy) abuse on the rate of cerebral serotonin synthesis Journal of Neurochemistry December 1, 2014
- Interactions between 3,4-Methylenedioxymethamphetamine and Ethanol in Humans and Rodents Neuropsychobiology 2009
Cites 24
- 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
- Human Pharmacology of MDMA Therapeutic Drug Monitoring March 19, 2004
- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
- Reorganization of ascending 5-HT axon projections in animals previously exposed to the recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") Journal of Neuroscience August 1, 1995
and 19 more in the library