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Archives of Toxicology

, Volume 91, Issue 10, pp 3373–3384 | Cite as

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

  • Michaela Fujáková-LipskiEmail author
  • Daniel KapingEmail author
  • Jana Šírová
  • Jiří Horáček
  • Tomáš Páleníček
  • Petr Zach
  • Jan Klaschka
  • Petr Kačer
  • Kamila Syslová
  • Monika Vrajová
  • Věra Bubenikova-Valešová
  • Christian Beste
  • Romana Šlamberová
Molecular Toxicology

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.

Keywords

Prenatal drug exposure Methamphetamine Neurotransmitters In-vivo microdialysis Rats 

Notes

Acknowledgements

This work was supported from the project “Sustainability for the National Institute of Mental Health”, under Grant Number LO1611, with a financial support from the Ministry of Education, Youth and Sports of the Czech Republic under the NPU I program, Grant GA 14-3708S from Grant Agency of the Czech Republic, Charles University Research Development Schemes—Progres Q35, institutional support RVO:67985807 and Specific Academic Research 260388/SVV/2017 from Charles University in Prague.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Michaela Fujáková-Lipski
    • 1
    • 7
    Email author
  • Daniel Kaping
    • 1
    • 5
    Email author
  • Jana Šírová
    • 1
    • 5
    • 7
  • Jiří Horáček
    • 1
  • Tomáš Páleníček
    • 1
  • Petr Zach
    • 2
  • Jan Klaschka
    • 3
  • Petr Kačer
    • 1
  • Kamila Syslová
    • 4
  • Monika Vrajová
    • 1
  • Věra Bubenikova-Valešová
    • 1
  • Christian Beste
    • 1
    • 5
  • Romana Šlamberová
    • 6
  1. 1.National Institute of Mental HealthKlecanyCzech Republic
  2. 2.Department of Anatomy, Third Faculty of MedicineCharles UniversityPragueCzech Republic
  3. 3.Department of Medical Informatics and BiostatisticsInstitute of Computer Science, The Czech Academy of SciencesPragueCzech Republic
  4. 4.Department of Organic TechnologyUniversity of Chemistry and TechnologyPragueCzech Republic
  5. 5.Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of MedicineTU DresdenDresdenGermany
  6. 6.Department of Normal, Pathological and Clinical Physiology, Third Faculty of MedicineCharles UniversityPragueCzech Republic
  7. 7.Third Faculty of MedicineCharles UniversityPragueCzech Republic

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