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.
Highlights
Mephedrone (4-methylmethcathinone) is a synthetic ringsubstituted cathinone often marketed as ‘‘bath salt’’
It is important to note that all mephedrone schedules induced the occurrence, in some animals, of a stereotypy that continued with self-bites and led to the appearance of injuries in that zone
Based on its structural similarity to well established neurotoxic psychostimulants such as methamphetamine and MDMA, it was hypothesized that mephedrone would exert neuronal damage
Summary
Mephedrone (4-methylmethcathinone) is a synthetic ringsubstituted cathinone often marketed as ‘‘bath salt’’. It appears to be used by people involved in the dance and music scene and used more broadly by many young adults and adolescents [1]. Different authors [12,13,14] have shown that mephedrone administration to rats increases extracellular dopamine (DA) and serotonin (5-HT) in rat brain, similar to the effects of MDMA. All these results evidenced that this drug interacts with DA and 5-HT transporters displaying a similar pattern to other amphetamine derivatives
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