Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[ 18 F]-ADAM/small-animal PET study

Shih, Jui‐Hu; Ma, Kuo‐Hsing; Chen, Chien-Fu F.; Cheng, Cheng‐Yi; Pao, Li-Heng; Weng, Shao-Ju; Huang, Yuahn-Sieh; Shiue, Chyng‐Yann; Yeh, Ming–Kung; Li, I‐Hsun

doi:10.1016/j.euroneuro.2015.11.001

Cited by 19 publications

(19 citation statements)

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“…Thus, MDMA can trigger a rapid pre-synaptic accumulation of hydrogen peroxide, a product of 5-HT metabolism involving monoamine oxidase B (MAO-B)1362. Hydrogen peroxide can be converted into hydroxyl radical to cause oxidative stress in mitochondria of the serotonergic neurons91363. Therefore, a potential therapeutic strategy against MDMA-induced serotonergic neurotoxicity is using selective serotine reuptake inhibitors (SSRIs) to prevent MDMA from entering the pre-synaptic terminals64.…”

Section: Discussionmentioning

confidence: 99%

“…We also found that MDMA induced neurite damage and neuron death in serotonergic neuron in vitro 30. Moreover, resveratrol, a natural polyphenolic phytoalexin, could protected against MDMA-induced decrease in SERT availability in midbrain and thalamus of rats9. In the present study, SERT density of different brain regions of the monkey (macaca cyclopis ) were assessed based on the uptakes of [ 123 I]-ADAM using single photon emission computerized tomography (SPECT).…”

mentioning

confidence: 84%

“…Recent studies have shown that MDMA chronically inhibits neocortical serotonin signaling in parallel with hyperthermia345 and causes deficits in prospective memory and/or social intelligence6. Animal studies have demonstrated that repeated administration of MDMA results in clusters of aberrant serotonergic fibers7 and affects the serotonergic neurotransmitter system in an association with reduced density of cerebral serotonin transporters (SERT) in the brain89. Regarding serotonergic pathway of brain, MDMA alters serotonin (5-HT), 5-HT receptors, and SERT levels910.…”

mentioning

confidence: 99%

“…Animal studies have demonstrated that repeated administration of MDMA results in clusters of aberrant serotonergic fibers7 and affects the serotonergic neurotransmitter system in an association with reduced density of cerebral serotonin transporters (SERT) in the brain89. Regarding serotonergic pathway of brain, MDMA alters serotonin (5-HT), 5-HT receptors, and SERT levels910. MDMA is known to have a high affinity to α-adrenergic and nicotinic receptors (e.g.…”

mentioning

confidence: 99%

“…The involvement of SERT in the pathological mechanism of MDMA has been well documented, along with therapeutic drugs to protect against MDMA-induced neurotoxicity9141516. Dextromethorphan (DM, 3-methoxy-17-methylmorphinan) is a typical morphine like opioid, which is derived from levorphanol17.…”

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confidence: 99%

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Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

Hsing

Liu

Weng

et al. 2016

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3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [123I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [123I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [123I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate.

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Section: Discussionmentioning

confidence: 99%

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confidence: 84%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

Hsing

Liu

Weng

et al. 2016

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Potential of Polyphenols in the Treatment of Major Depression

Dhir

2017

Neuroprotective Effects of Phytochemicals in Neurological Disorders

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MDMA and memory, addiction, and depression: dose-effect analysis

et al. 2022

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Rationale ±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that shows substantial promise as a psychotherapeutic agent. Still, there is some concern regarding its behavioral toxicity, and its dose-effect relationship is poorly understood. We previously explored the role of dose in the cognitive effects of MDMA in a systematic review of existing literature and found no evidence in animals that MDMA impairs memory at low doses (< 3 mg/kg) but mixed results at high doses (≥ 3 mg/kg). Since this review comprised mostly of single-dose studies and an assortment of methodologies, an empirical dose-ranging study on this topic is warranted. Objectives The current study aims to evaluate the conclusion from our systematic review that 3 mg/kg may be the threshold for MDMA-induced amnesia, and to further understand the dose-effect relationship of MDMA on behavioral assays of memory, addiction, and depression. Methods We systematically examined the effects of 0.01 to 10 mg/kg MDMA on Pavlovian fear conditioning; behavioral sensitization, conditioned place preference, and conditioned responding; and the Porsolt forced swim test in mice. Results High doses of MDMA (≥ 3 mg/kg) produced amnesia of fear conditioning memory, some evidence of an addictive potential, and antidepressant effects, while low doses of MDMA (≤ 1 mg/kg) had no effect on these behaviors. Conclusions The present dose-ranging study provides further evidence that 3 mg/kg is the threshold for MDMA-induced amnesia. These findings, in addition to our systematic review, demonstrate that careful selection of MDMA dose is critical. High doses (≥ 3 mg/kg) should likely be avoided due to evidence that they can produce amnesia and addiction. Conversely, there is little evidence to suggest that low doses, which are usually administered in clinical studies (approximately 1–2 mg/kg), will lead to these same adverse effects. Ultra-low doses (< 1 mg/kg) are likely even safer and should be investigated for therapeutic effects in future studies.

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Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[ 18 F]-ADAM/small-animal PET study

Cited by 19 publications

References 66 publications

Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

Potential of Polyphenols in the Treatment of Major Depression

MDMA and memory, addiction, and depression: dose-effect analysis

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