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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.
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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