Abstract
Mephedrone is a drug of abuse marketed as 'bath salts". There are discrepancies concerning its long-term effects. We have investigated the neurotoxicity of mephedrone in mice following different exposition schedules. Schedule 1: four doses of 50 mg/kg. Schedule 2: four doses of 25 mg/kg. Schedule 3: three daily doses of 25 mg/kg, for two consecutive days. All schedules induced, in some animals, an aggressive behavior and hyperthermia as well as a decrease in weight gain. Mephedrone (schedule 1) induced dopaminergic and serotoninergic neurotoxicity that persisted 7 days after exposition. At a lower dose (schedule 2) only a transient dopaminergic injury was found. In the weekend consumption pattern (schedule 3), mephedrone induced dopamine and serotonin transporter loss that was accompanied by a decrease in tyrosine hydroxylase and tryptophan hydroxylase 2 expression one week after exposition. Also, mephedrone induced a depressive-like behavior, as well as a reduction in striatal D2 density, suggesting higher susceptibility to addictive drugs. In cultured cortical neurons, mephedrone induced a concentration-dependent cytotoxic effect. Using repeated doses for 2 days in an elevated ambient temperature we evidenced a loss of frontal cortex dopaminergic and hippocampal serotoninergic neuronal markers that suggest injuries at nerve endings.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic Agents / toxicity*
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Animals
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Body Temperature / drug effects
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Cell Survival / drug effects
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Cells, Cultured
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Corpus Striatum / metabolism
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Dopamine Plasma Membrane Transport Proteins / metabolism
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Dose-Response Relationship, Drug
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Frontal Lobe / metabolism
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Hippocampus / metabolism
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Male
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Methamphetamine / analogs & derivatives*
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Methamphetamine / toxicity
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Mice
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism
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Serotonin Plasma Membrane Transport Proteins / metabolism
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Time Factors
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Tryptophan Hydroxylase / metabolism
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Tyrosine 3-Monooxygenase / metabolism
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Weight Gain / drug effects
Substances
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Adrenergic Agents
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Dopamine Plasma Membrane Transport Proteins
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Serotonin Plasma Membrane Transport Proteins
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Methamphetamine
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mephedrone
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Tyrosine 3-Monooxygenase
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Tph2 protein, mouse
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Tryptophan Hydroxylase
Grants and funding
Funding for this study was provided by grants from Generalitat de Catalunya (SGR977), Plan Nacional sobre Drogas (2010/005; 2012/102) and Ministerio de Ciencia e Innovación (SAF2010-15948). Martínez-Clemente is a recipient of a fellowship from the Plan Nacional sobre Drogas and López-Arnau is a recipient of a fellowship from Generalitat de Catalunya. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.