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

  • Molecular Toxicology
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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.

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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.

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    Authors and Affiliations

    1. National Institute of Mental Health, Klecany, Czech Republic

      Michaela Fujáková-Lipski, Daniel Kaping, Jana Šírová, Jiří Horáček, Tomáš Páleníček, Petr Kačer, Monika Vrajová, Věra Bubenikova-Valešová & Christian Beste

    2. Department of Anatomy, Third Faculty of Medicine, Charles University, Prague, Czech Republic

      Petr Zach

    3. Department of Medical Informatics and Biostatistics, Institute of Computer Science, The Czech Academy of Sciences, Prague, Czech Republic

      Jan Klaschka

    4. Department of Organic Technology, University of Chemistry and Technology, Prague, Czech Republic

      Kamila Syslová

    5. Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Dresden, Germany

      Daniel Kaping, Jana Šírová & Christian Beste

    6. Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic

      Romana Šlamberová

    7. Third Faculty of Medicine, Charles University, Prague, Czech Republic

      Michaela Fujáková-Lipski & Jana Šírová

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    Fujáková-Lipski, M., Kaping, D., Šírová, J. et al. Trans-generational neurochemical modulation of methamphetamine in the adult brain of the Wistar rat. Arch Toxicol 91, 3373–3384 (2017). https://doi.org/10.1007/s00204-017-1969-y

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