Metformin Prevented Dopaminergic Neurotoxicity Induced by 3,4-Methylenedioxymethamphetamine Administration.
Pier Francesca Porceddu, Ismail Ogunbayode Ishola, Liliana Contu, Micaela Morelli
Neurotoxicity Research July 2016 DOI: 10.1007/s12640-016-9633-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal (mouse) experimental study Peer reviewed |
|---|---|
| Population | Adult mice |
| Interventions | Metformin MDMA |
| Dose | Metformin 2 × 200 mg/kg orally (1 h before first MDMA and 4 h after last MDMA), then 1 × 200 mg/kg on days 2 and 3; MDMA 4 × 20 mg/kg intraperitoneally at 2-h intervals |
| Duration | Assessments at 48 hours and 7 days after the last MDMA administration |
| Measures | Dopamine transporter (DAT) immunohistochemistry, tyrosine hydroxylase (TH) immunohistochemistry |
| Topics | MDMA |
| Keywords | Caudate putamen Neurodegeneration Neuroprotection Substantia nigra Tyrosine hydroxylase |
| Key findings | Metformin prevented MDMA-induced loss of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta and of tyrosine hydroxylase- and dopamine transporter-positive fibers in the caudate putamen at both 48 hours and 7 days after the last MDMA dose. The authors conclude that metformin is neuroprotective against short- and long-lasting dopaminergic neurodegeneration caused by MDMA. |
Abstract
Metformin, a well-known antidiabetic drug, has recently been proposed to promote neurogenesis and to have a neuroprotective effect on the neurodegenerative processes induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in models of Parkinson's disease. Interestingly, metformin has antioxidant properties and is involved in regulating the production of cytokines released during the neuroinflammatory process. Several studies have reported that 3,4-methylenedioxymethamphetamine (MDMA), a recreational drug mostly consumed by young adults, produces a persistent loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and caudate putamen (CPu) of mice. The aim of this study was to investigate the potential neuroprotective effect of metformin against short- and long-term neurotoxicity induced by MDMA and its role on MDMA-induced hyperthermia. Adult mice received metformin (2 × 200 mg/kg, 11-h intervals, administered orally), MDMA (4 × 20 mg/kg, 2-h interval, administered intraperitoneally), or MDMA plus metformin (2 × 200 mg/kg, 1 h before the first MDMA administration and 4 h after the last). On the second and third day, mice were treated with vehicle or metformin (1 × 200 mg/kg) and sacrificed 48 h and 7 days after the last MDMA administration. The neuroprotective effect of metformin on MDMA-induced dopaminergic damage was evaluated by dopamine transporter (DAT) and tyrosine hydroxylase (TH) immunohistochemistry in SNc and CPu. Metformin prevented the MDMA-induced loss of TH-positive neurons in the SNc and TH- and DAT-positive fibers in CPu, both at 48 h and 7 days after the last MDMA administration. These results show that metformin is neuroprotective against the short- and long-lasting dopaminergic neurodegeneration induced by MDMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- Dopamine D2-receptor knockout mice are protected against dopaminergic neurotoxicity induced by methamphetamine or MDMA Neurobiology of Disease March 22, 2021
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and 13 more in the library