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Dose and time-dependent selective neurotoxicity induced by mephedrone in mice.
Martínez-Clemente, José; López-Arnau, Raúl; Abad, Sonia; Pubill Sánchez, David; Escubedo Rafa, Elena; Camarasa García, Jordi
Universitat de Barcelona
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.
22-07-2014
Amfetamines
Lòbul frontal
Neurotoxicologia
Ratolins (Animals de laboratori)
Sistema nerviós central
Amphetamines
Frontal lobe
Neurotoxicology
Mice (Laboratory animals)
Central nervous system
cc-by (c) Martínez-Clemente, José et al., 2014
http://creativecommons.org/licenses/by/3.0/es
Artículo
info:eu-repo/semantics/publishedVersion
Public Library of Science (PLoS)
         

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