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Repeated doses of methylone, a new drug of abuse, induce changes in serotonin and dopamine systems in the mouse

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Abstract

Rationale

Methylone, a new drug of abuse sold as “bath salts,” has similar effects to ecstasy or cocaine.

Objective

We have investigated changes in dopaminergic and serotoninergic markers, indicative of neuronal damage induced by methylone in the frontal cortex, hippocampus, and striatum of mice, according to two different treatment schedules.

Methods

Methylone was given subcutaneously to male Swiss CD1 mice at an ambient temperature of 26 °C. Treatment A consisted of three doses of 25 mg/kg at 3.5-h intervals between doses for two consecutive days, and treatment B consisted of four doses of 25 mg/kg at 3-h intervals in 1 day.

Results

Repeated methylone administration induced hyperthermia and a significant loss in body weight. Following treatment A, methylone induced transient dopaminergic (frontal cortex) and serotoninergic (hippocampus) impairment. Following treatment B, transient dopaminergic (frontal cortex) and serotonergic (frontal cortex and hippocampus) changes 7 days after treatment were found. We found evidence of astrogliosis in the CA1 and the dentate gyrus of the hippocampus following treatment B. The animals also showed an increase in immobility time in the forced swim test, pointing to a depressive-like behavior. In cultured cortical neurons, methylone (for 24 and 48 h) did not induce a remarkable cytotoxic effect.

Conclusions

The neural effects of methylone differ depending upon the treatment schedule. Neurochemical changes elicited by methylone are apparent when administered at an elevated ambient temperature, four times per day at 3-h intervals, which is in accordance with its short half-life.

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Acknowledgments

The authors acknowledge C. Roberts for language revision of the manuscript. This study was supported by grants from the Plan Nacional sobre Drogas (2010/005 and 2012/102), the Ministerio de Ciencia e Innovación (SAF2010-15948), and the Generalitat de Catalunya (SGR977). López-Arnau is a recipient of a fellowship from Generalitat de Catalunya. Martínez-Clemente is a recipient of a fellowship from the Plan Nacional sobre Drogas, and Abad is a recipient of a fellowship from IBUB.

Conflict of interest

The authors declare that they have no financial or commercial conflicts of interest.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section) and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain

    Raúl López-Arnau, José Martínez-Clemente, Sonia Abad, David Pubill, Jorge Camarasa & Elena Escubedo

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  1. Raúl López-Arnau
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  2. José Martínez-Clemente
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  3. Sonia Abad
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  4. David Pubill
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  5. Jorge Camarasa
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  6. Elena Escubedo
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Corresponding author

Correspondence to Jorge Camarasa.

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López-Arnau, R., Martínez-Clemente, J., Abad, S. et al. Repeated doses of methylone, a new drug of abuse, induce changes in serotonin and dopamine systems in the mouse. Psychopharmacology 231, 3119–3129 (2014). https://doi.org/10.1007/s00213-014-3493-6

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  • DOI: https://doi.org/10.1007/s00213-014-3493-6

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