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Title: Dose and time-dependent selective neurotoxicity induced by mephedrone in mice.
Author: Martínez-Clemente, José
López-Arnau, Raúl
Abad, Sonia
Pubill Sánchez, David
Escubedo Rafa, Elena
Camarasa García, Jordi
Keywords: Amfetamines
Lòbul frontal
Ratolins (Animals de laboratori)
Sistema nerviós central
Frontal lobe
Mice (Laboratory animals)
Central nervous system
Issue Date: 3-Jun-2014
Publisher: Public Library of Science (PLoS)
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.
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It is part of: PLoS One, 2014, vol. 9, num. 6, p. e99002
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

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