Limits...
Dose and time-dependent selective neurotoxicity induced by mephedrone in mice.

Martínez-Clemente J, López-Arnau R, Abad S, Pubill D, Escubedo E, Camarasa J - PLoS ONE (2014)

Bottom Line: At a lower dose (schedule 2) only a transient dopaminergic injury was found.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section) and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.

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.

Show MeSH

Related in: MedlinePlus

Effect of a mephedrone exposure (4 doses of 25 mg/kg, s.c. at 2 h interval) on dopamine transporter density, measured as [3H]WIN35428 binding in mouse striatum (A), or frontal cortex (B) and 5-HT transporter density, measured as [3H]paroxetine binding, in hippocampus (C) and frontal cortex (D).Results are expressed as mean±S.E.M. from 8–10 animals. **p<0.01 vs. saline.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4043985&req=5

pone-0099002-g002: Effect of a mephedrone exposure (4 doses of 25 mg/kg, s.c. at 2 h interval) on dopamine transporter density, measured as [3H]WIN35428 binding in mouse striatum (A), or frontal cortex (B) and 5-HT transporter density, measured as [3H]paroxetine binding, in hippocampus (C) and frontal cortex (D).Results are expressed as mean±S.E.M. from 8–10 animals. **p<0.01 vs. saline.

Mentions: Schedule 2: 3 days after the drug regimen, the frontal cortex was the only area where a marker showed a significant decrease. For this reason, the specific binding of [3H]WIN35428 in this area, was also evaluated 4 days later. At this time, DA transporter density returned to basal levels (Fig. 2B). Mephedrone did not modify [3H]WIN35428 binding in the striatum (Fig. 2A) or the [3H]paroxetine binding neither in the hippocampus nor in the frontal cortex (Fig. 2C and 2D).


Dose and time-dependent selective neurotoxicity induced by mephedrone in mice.

Martínez-Clemente J, López-Arnau R, Abad S, Pubill D, Escubedo E, Camarasa J - PLoS ONE (2014)

Effect of a mephedrone exposure (4 doses of 25 mg/kg, s.c. at 2 h interval) on dopamine transporter density, measured as [3H]WIN35428 binding in mouse striatum (A), or frontal cortex (B) and 5-HT transporter density, measured as [3H]paroxetine binding, in hippocampus (C) and frontal cortex (D).Results are expressed as mean±S.E.M. from 8–10 animals. **p<0.01 vs. saline.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043985&req=5

pone-0099002-g002: Effect of a mephedrone exposure (4 doses of 25 mg/kg, s.c. at 2 h interval) on dopamine transporter density, measured as [3H]WIN35428 binding in mouse striatum (A), or frontal cortex (B) and 5-HT transporter density, measured as [3H]paroxetine binding, in hippocampus (C) and frontal cortex (D).Results are expressed as mean±S.E.M. from 8–10 animals. **p<0.01 vs. saline.
Mentions: Schedule 2: 3 days after the drug regimen, the frontal cortex was the only area where a marker showed a significant decrease. For this reason, the specific binding of [3H]WIN35428 in this area, was also evaluated 4 days later. At this time, DA transporter density returned to basal levels (Fig. 2B). Mephedrone did not modify [3H]WIN35428 binding in the striatum (Fig. 2A) or the [3H]paroxetine binding neither in the hippocampus nor in the frontal cortex (Fig. 2C and 2D).

Bottom Line: At a lower dose (schedule 2) only a transient dopaminergic injury was found.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section) and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.

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.

Show MeSH
Related in: MedlinePlus