Mephedrone exposure in adolescent rats alters the rewarding effect of morphine in adults

Eur J Pharmacol. 2017 Sep 5:810:63-69. doi: 10.1016/j.ejphar.2017.06.007. Epub 2017 Jun 8.

Abstract

An increasing number of data show that exposure to mephedrone in adolescence can have long-lasting implication on brain activity and on peripheral organs/tissues. The aim of this study was to investigate whether adolescent exposure to mephedrone (10mg/kg, i.p.) has influence upon the rewarding effect of morphine (5mg/kg, i.p.) in adult rats. Thus, the adolescent rats (on the 30th PND) were treated with mephedrone for 7 consecutive days. When the animals were adult (on the 60th PND) the morphine-induced conditioned place preference (CPP) test was performed. After that, the level of DNA methylation in the striatum was investigated. DNA methylation is one of the epigenetic mechanisms which produces changes in the genome. These alterations may affect the phenotype, without effect on DNA sequences, and has influence on drug addiction. Additionally, in order to check the toxic properties of mephedrone on the peripheral organs, the histopathological examination of kidney and liver was carried out. The present experiments demonstrated that: 1) adolescent mephedrone exposure may intensify the rewarding effect of morphine in adult rats in the CPP test; 2) mephedrone may induce the alterations in DNA methylation in striatum of adult rats leading to changes in gene activity; 3) mephedrone may produce some retrogressive disturbances in kidney and liver, which confirms the toxic properties of this substance.

Keywords: Conditioned place preference test; Epigenetic changes; Histopathological examination; Legal highs; Opioid drugs.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • DNA Methylation / drug effects
  • Liver / cytology
  • Liver / drug effects
  • Locomotion / drug effects
  • Methamphetamine / analogs & derivatives*
  • Methamphetamine / pharmacology
  • Morphine / pharmacology*
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Rats
  • Rats, Wistar
  • Reward*
  • Time Factors

Substances

  • Methamphetamine
  • Morphine
  • mephedrone