Repeated doses of methylone, a new drug of abuse, induce changes in serotonin and dopamine systems in the mouse.
BACKGROUND
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.
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
R
López-Arnau
José
J
Martínez-Clemente
Sonia
S
Abad
David
D
Pubill
Jorge
J
Camarasa
Elena
E
Escubedo
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000139:chemically induced / Q000523:psychology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000473:pathology / Q000523:psychology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013550:Swimming / Q000523:psychology; D015431:Weight Loss / Q000187:drug effects
D000697:Central Nervous System Stimulants; D012701:Serotonin; D008694:Methamphetamine; C400939:methylone; D004298:Dopamine