Trans-generational neurochemical modulation of methamphetamine in the adult brain of the Wistar rat

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Michaela Fujáková-Lipski - , National Institute of Mental Health, Charles University Prague (Author)
  • Daniel Kaping - , National Institute of Mental Health, Department of Child and Adolescent Psychiatry and Psychotherapy (Author)
  • Jana Šírová - , National Institute of Mental Health, Charles University Prague, Department of Child and Adolescent Psychiatry and Psychotherapy (Author)
  • Jiří Horáček - , National Institute of Mental Health (Author)
  • Tomáš Páleníček - , National Institute of Mental Health (Author)
  • Petr Zach - , Charles University Prague (Author)
  • Jan Klaschka - , Czech Academy of Sciences (Author)
  • Petr Kačer - , National Institute of Mental Health (Author)
  • Kamila Syslová - , University of Chemistry and Technology, Prague (Author)
  • Monika Vrajová - , National Institute of Mental Health (Author)
  • Věra Bubenikova-Valešová - , National Institute of Mental Health (Author)
  • Christian Beste - , Department of Child and Adolescent Psychiatry and Psychotherapy, National Institute of Mental Health (Author)
  • Romana Šlamberová - , Charles University Prague (Author)

Abstract

Chronic methamphetamine (METH) abuse has been shown to elicit strong neurotoxic effects. Yet, with an increasing number of children born to METH abusing mothers maturing into adulthood, one important question is how far do the neurotoxic effects of METH alter various neurotransmitter systems in the adult METH-exposed offspring. The purpose of this study was to investigate long-term trans-generational neurochemical changes, following prenatal METH exposure, in the adult Wistar rat brain. METH or saline (SAL—control animals) was administered to pregnant dams throughout the entire gestation period (G0-G22). At postnatal day 90, dopamine, serotonin, glutamate and GABA were measured in the adult brain before (baseline) and after a METH re-administration using in vivo microdialysis and liquid chromatography/mass spectrometry. The results show that METH-exposure increased basal levels of monoamines and glutamate, but decreased GABA levels in all measured brain regions. Acute challenge with METH injection in the METH-exposed group induced a lower increase in the monoamine system relative to the increase in the GABAergic and glutamatergic system. The data show that prenatal METH exposure has strong effects on the monoaminergic, GABAergic and glutamatergic system even when exposure to METH was limited to the prenatal phase. Toxicological effects of METH have therefore longer lasting effects as currently considered and seem to affect the excitatory-inhibitory balance in the brain having strong implications for cognitive and behavioral functioning.

Details

Original languageEnglish
Pages (from-to)3373-3384
Number of pages12
JournalArchives of toxicology
Volume91
Issue number10
Publication statusPublished - 1 Oct 2017
Peer-reviewedYes

External IDs

PubMed 28477265
ORCID /0000-0002-2989-9561/work/160952487

Keywords

Keywords

  • In-vivo microdialysis, Methamphetamine, Neurotransmitters, Prenatal drug exposure, Rats