Global Ethanol-Induced Enhancements of Monoaminergic Neurotransmission: A Meta-Analysis Study

Authors

  • Ines Brand,

    1. Institute of Psychopharmacology , Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany
    Search for more papers by this author
  • Sarah Fliegel,

    1. Institute of Psychopharmacology , Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany
    Search for more papers by this author
  • Rainer Spanagel,

    1. Institute of Psychopharmacology , Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany
    Search for more papers by this author
  • Hamid R. Noori

    Corresponding author
    1. Institute of Psychopharmacology , Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany
    • Reprint requests: Hamid R. Noori, Institute of Psychopharmacology, Central Institute of Mental Health (CIMH), Medical Faculty Mannheim/Heidelberg University, J5, 68159 Mannheim, Germany; Tel.: +49-621-1703-6289; Fax: +49-621-1703 6255; E-mail: hamid.noori@zi-mannheim.de

    Search for more papers by this author

Abstract

Background

Numerous studies use in vivo microdialysis as a quantification method for studying dynamical alterations of extracellular neurotransmitter concentrations in specific brain regions of various species following acute and chronic administration of ethanol (EtOH). A major focus of these investigations is the EtOH-induced effects on the neurochemistry of forebrain regions, particularly dose-dependent neuroadaptive changes of monoamine systems.

Methods

Here, we performed a meta-analysis on published data sets of in vivo microdialysis measurements to assess the concentration-dependent effects of EtOH on monoamine levels within 19 distinct brain regions in adult rats, which were identified as major components of a neurocircuitry for modeling drug effects. In total, data sets of 210 research articles (7,407 rats) were analyzed.

Results

The analysis of the basal values of noradrenaline, serotonin, and dopamine in those regions indicated hardly any dependencies on gender, strain, or state of consciousness. However, the acute administrations of EtOH (intraperitoneal 0.25 to 2.5 g/kg) appear to increase the level of monoamines globally and independent of the brain sites up to 270% of the basal concentrations. Moreover, a peak time average of approximately 40 minutes suggests an optimal time interval of maximal 240 minutes length to completely study the effects of different doses of EtOH within the framework of microdialysis experiments. The analysis further revealed a positive correlation between the magnitude of increase (peak % baseline) of local extracellular monoamine concentrations and the applied doses of EtOH, while the temporal occurrence of the EtOH-induced peaks in the concentrations (peak time) was mostly negatively correlated.

Conclusions

Our results provide a universal database and framework for the optimal design of future in vivo microdialysis and in silico experiments in neurochemistry and pharmacology.

Ancillary