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Title: Neuronal changes and oxidative stress in adolescent rats after repeated exposure to mephedrone

Mephedrone is a new designer drug of abuse. We have investigated the neurochemical/enzymatic changes after mephedrone administration to adolescent rats (3 × 25 mg/kg, s.c. in a day, with a 2 h interval between doses, for two days) at high ambient temperature (26 ± 2 °C), a schedule that intends to model human recreational abuse. In addition, we have studied the effect of mephedrone in spatial learning and memory. The drug caused a transient decrease in weight gain. After the first dose, animals showed hypothermia but, after the subsequent doses, temperature raised over the values of saline-treated group. We observed the development of tolerance to these thermoregulatory effects of mephedrone. Mephedrone induced a reduction of the densities of dopamine (30% in the frontal cortex) and serotonin (40% in the frontal cortex and the hippocampus and 48% in the striatum) transporters without microgliosis. These deficits were also accompanied by a parallel decrease in the expression of tyrosine hydroxylase and tryptophan hydroxylase 2. These changes matched with a down-regulation of D{sub 2} dopamine receptors in the striatum. Mephedrone also induced an oxidative stress evidenced by an increase of lipid peroxidation in the frontal cortex, and accompanied by a rise in glutathione peroxidasemore » levels in all studied brain areas. Drug-treated animals displayed an impairment of the reference memory in the Morris water maze one week beyond the cessation of drug exposure, while the spatial learning process seems to be preserved. These findings raise concerns about the neuronal long-term effects of mephedrone. - Highlights: • We studied the dopaminergic and serotonergic neurotoxicity of mephedrone in rats. • Mephedrone induced a transient hypothermia following sustained hyperthermia. • In a weekend consumption pattern, mephedrone induced selective neurotoxicity. • Mephedrone generated oxidative stress. • Mephedrone induced an impairment in memory function.« less
Authors:
;  [1] ;  [2] ;  [3] ;  [1] ;  [2] ;  [1] ;  [2] ;  [1] ;  [2]
  1. Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain)
  2. (IBUB), Faculty of Pharmacy, University of Barcelona (Spain)
  3. Animal Experimentation Unit of Psychology and Pharmacy, University of Barcelona (Spain)
Publication Date:
OSTI Identifier:
22465778
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 286; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CATALASE; DOPAMINE; GLUTATHIONE; HIPPOCAMPUS; HYDROXYLASES; HYPERTHERMIA; HYPOTHERMIA; IMMUNOGLOBULINS; LIPIDS; OXIDATION; RATS; RECEPTORS; SEROTONIN; STRESSES; SUPEROXIDE DISMUTASE; TRYPTOPHAN; TYROSINE