Study on the neuroprotective effect of fluoxetine against MDMA-induced neurotoxicity on the serotonin transporter in rat brain using micro-PET

Li, I‐Hsun; Huang, Wen-Sheng; Shiue, Chyng‐Yann; Huang, Ya-Yao; Liu, Ren-Shyan; Chyueh, San‐Chong; Hu, Shih-Hsiung; Liao, Mei-Hsiu; Shen, Lie-Hang; Liu, Jiang-Chuan; Ma, Kuo‐Hsing

doi:10.1016/j.neuroimage.2009.07.072

Cited by 50 publications

(52 citation statements)

References 61 publications

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“…A number of studies have suggested that SERT is highly involved in MDMA-induced neurotoxicity13585960. The binding of MDMA to SERT of the 5-HT nerve terminal leads to the release of 5-HT from the storage vesicles61 and causes an acute increase in 5-HT level in the pre-synaptic neuron.…”

Section: Discussionmentioning

confidence: 99%

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

Sci Rep

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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%

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

Sci Rep

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“…We also examined if fluoxetine could protect the P19 neurons against MDMA-induced toxicity since the protective effects of fluoxetine to serotonergic neurotoxicity were observed in the brain [70,71]. However, the compound did not have protective effects in our cell model.…”

Section: Discussionmentioning

confidence: 99%

Non-Serotonergic Neurotoxicity by MDMA (Ecstasy) in Neurons Derived from Mouse P19 Embryonal Carcinoma Cells

et al. 2016

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3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays. The P19-derived neurons express both the serotonin reuptake transporter (SERT), that is functionally active, and the serotonin metabolizing enzyme monoamine oxidase A (MAO-A). The involvement of these proteins in the MDMA-induced toxicity was investigated by a pharmacological approach. The MAO inhibitors clorgyline and deprenyl, and the SERT inhibitor fluoxetine, per se or in combination, were not able to mimic the toxic effects of MDMA in the P19-derived neurons or block the MDMA-induced cell toxicity. Oxidative stress has been implicated in MDMA-induced neurotoxicity, but pre-treatment with the antioxidants α-tocopherol or N-acetylcysteine did not reveal any protective effects in the P19 neurons. Involvement of mitochondria in the MDMA-induced cytotoxicity was also examined, but MDMA did not alter the mitochondrial membrane potential (ΔΨm) in the P19 neurons. We conclude that MDMA produce a concentration-, time- and temperature-dependent neurotoxicity and our results suggest that the mechanism behind MDMA-induced toxicity in mouse-derived neurons do not involve the serotonergic system, oxidative stress or mitochondrial dysfunction.

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“…A cylinder calibration method was used to convert the image units from cps per voxel (cps/voxel) to nCi per cm3 (nCi/cm3). Finally, the CT scan was performed by the same machine[17], [18].…”

Section: Methodsmentioning

confidence: 99%

Manipulation Therapy Prior to Diagnosis Induced Primary Osteosarcoma Metastasis—From Clinical to Basic Research

Wang

Chen

et al. 2014

PLoS ONE

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Osteosarcoma (OS) patients who suffer manipulation therapy (MT) prior to diagnosis resulted in poor prognosis with increasing metastasis or recurrence rate. The aim of the study is to establish an in vivo model to identify the effects of MT on OS. The enrolled 235 OS patients were followed up in this study. In vivo nude mice model with tibia injection of GFP-labeled human OS cells were randomly allocated into MT(+) that with repeated massage on tumor site twice a week and no treatment as MT(−) group. The five-year survival, metastasis and recurrence rates were recorded in clinical subjects. X-ray plainfilm, micro-PET/CT scan, histopathology, serum metalloproteinase 2 (MMP2), metalloproteinase 9 (MMP9) level and human kinase domain insert receptor (KDR) pattern were assayed in mice model. The results showed that patient with MT decreased 5-year survival and higher recurrence or metastasis rate. Compatible with clinical findings, the decreased body weight (30.5±0.65 g) and an increased tumor volume (8.3±1.18 mm3) in MT(+) mice were observed. The increasing signal intensity over lymph node region of hind limb by micro-PET/CT and the tumor cells were detected in lung and bilateral lymph nodes only in MT(+) group. MMP2 (214±9.8 ng/ml) and MMP9 (25.5±1.81 ng/ml) were higher in MT(+) group than in MT(−) group (165±7.8 ng/ml and 16.9±1.40 ng/ml, individually) as well as KDR expression. Taking clinical observations and in vivo evidence together, MT treatment leads to poor prognosis of primary osteosarcoma; physicians should pay more attention on patients who seek MT before diagnosis.

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Study on the neuroprotective effect of fluoxetine against MDMA-induced neurotoxicity on the serotonin transporter in rat brain using micro-PET

Cited by 50 publications

References 61 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

Non-Serotonergic Neurotoxicity by MDMA (Ecstasy) in Neurons Derived from Mouse P19 Embryonal Carcinoma Cells

Manipulation Therapy Prior to Diagnosis Induced Primary Osteosarcoma Metastasis—From Clinical to Basic Research

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