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Ethanol-induced alterations of amino acids measured by in vivo microdialysis in rats: a meta-analysis.

Fliegel S, Brand I, Spanagel R, Noori HR - In Silico Pharmacol (2013)

Bottom Line: Specifically, glutamate in the nucleus accumbens shows a decreasing logarithmic dose response curve.In summary, our results provide standardized basal values for future experimental and in silico studies on neurotransmitter release in the rat brain and may be helpful to understand the effect of ethanol on neurotransmitter release.Furthermore, this study illustrates the benefit of meta-analyses using the generalization of a wide range of preclinical data.

View Article: PubMed Central - PubMed

Affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, J5, 68159 Mannheim, Germany.

ABSTRACT

Purpose: In recent years in vivo microdialysis has become an important method in research studies investigating the alterations of neurotransmitters in the extracellular fluid of the brain. Based on the major involvement of glutamate and γ-aminobutyric acid (GABA) in mediating a variety of alcohol effects in the mammalian brain, numerous microdialysis studies have focused on the dynamical behavior of these systems in response to alcohol.

Methods: Here we performed multiple meta-analyses on published datasets from the rat brain: (i) we studied basal extracellular concentrations of glutamate and GABA in brain regions that belong to a neurocircuitry involved in neuropsychiatric diseases, especially in alcoholism (Noori et al., Addict Biol 17:827-864, 2012); (ii) we examined the effect of acute ethanol administration on glutamate and GABA levels within this network and (iii) we studied alcohol withdrawal-induced alterations in glutamate and GABA levels within this neurocircuitry.

Results: For extraction of basal concentrations of these neurotransmitters, datasets of 6932 rats were analyzed and the absolute basal glutamate and GABA levels were estimated for 18 different brain sites. In response to different doses of acute ethanol administration, datasets of 529 rats were analyzed and a non-linear dose response (glutamate and GABA release) relationship was observed in several brain sites. Specifically, glutamate in the nucleus accumbens shows a decreasing logarithmic dose response curve. Finally, regression analysis of 11 published reports employing brain microdialysis experiments in 104 alcohol-dependent rats reveals very consistent augmented extracellular glutamate and GABA levels in various brain sites that correlate with the intensity of the withdrawal response were identified.

Conclusions: In summary, our results provide standardized basal values for future experimental and in silico studies on neurotransmitter release in the rat brain and may be helpful to understand the effect of ethanol on neurotransmitter release. Furthermore, this study illustrates the benefit of meta-analyses using the generalization of a wide range of preclinical data.

No MeSH data available.


Related in: MedlinePlus

The time course of withdrawal induced enhancements in the glutamate levels relative to the respective basal values in nucleus accumbens, caudate putamen and hippocampus. The time course was not provided for central amygdala.
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Fig4: The time course of withdrawal induced enhancements in the glutamate levels relative to the respective basal values in nucleus accumbens, caudate putamen and hippocampus. The time course was not provided for central amygdala.

Mentions: On the basis of our selection criteria for ethanol withdrawal, 11 articles (n = 104 rats) were extracted. All studies used freely moving male rats with a strain distribution of 55% Wistar and 45% Sprague Dawley animals. The experiments measured the amino acids alterations in an interval of [2; 12] hours after last exposure to alcohol within different brain regions (Table 7 and Figure 4) with significant enhancements of extracellular glutamate and GABA levels due to acute ethanol withdrawal.Table 7


Ethanol-induced alterations of amino acids measured by in vivo microdialysis in rats: a meta-analysis.

Fliegel S, Brand I, Spanagel R, Noori HR - In Silico Pharmacol (2013)

The time course of withdrawal induced enhancements in the glutamate levels relative to the respective basal values in nucleus accumbens, caudate putamen and hippocampus. The time course was not provided for central amygdala.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230485&req=5

Fig4: The time course of withdrawal induced enhancements in the glutamate levels relative to the respective basal values in nucleus accumbens, caudate putamen and hippocampus. The time course was not provided for central amygdala.
Mentions: On the basis of our selection criteria for ethanol withdrawal, 11 articles (n = 104 rats) were extracted. All studies used freely moving male rats with a strain distribution of 55% Wistar and 45% Sprague Dawley animals. The experiments measured the amino acids alterations in an interval of [2; 12] hours after last exposure to alcohol within different brain regions (Table 7 and Figure 4) with significant enhancements of extracellular glutamate and GABA levels due to acute ethanol withdrawal.Table 7

Bottom Line: Specifically, glutamate in the nucleus accumbens shows a decreasing logarithmic dose response curve.In summary, our results provide standardized basal values for future experimental and in silico studies on neurotransmitter release in the rat brain and may be helpful to understand the effect of ethanol on neurotransmitter release.Furthermore, this study illustrates the benefit of meta-analyses using the generalization of a wide range of preclinical data.

View Article: PubMed Central - PubMed

Affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, J5, 68159 Mannheim, Germany.

ABSTRACT

Purpose: In recent years in vivo microdialysis has become an important method in research studies investigating the alterations of neurotransmitters in the extracellular fluid of the brain. Based on the major involvement of glutamate and γ-aminobutyric acid (GABA) in mediating a variety of alcohol effects in the mammalian brain, numerous microdialysis studies have focused on the dynamical behavior of these systems in response to alcohol.

Methods: Here we performed multiple meta-analyses on published datasets from the rat brain: (i) we studied basal extracellular concentrations of glutamate and GABA in brain regions that belong to a neurocircuitry involved in neuropsychiatric diseases, especially in alcoholism (Noori et al., Addict Biol 17:827-864, 2012); (ii) we examined the effect of acute ethanol administration on glutamate and GABA levels within this network and (iii) we studied alcohol withdrawal-induced alterations in glutamate and GABA levels within this neurocircuitry.

Results: For extraction of basal concentrations of these neurotransmitters, datasets of 6932 rats were analyzed and the absolute basal glutamate and GABA levels were estimated for 18 different brain sites. In response to different doses of acute ethanol administration, datasets of 529 rats were analyzed and a non-linear dose response (glutamate and GABA release) relationship was observed in several brain sites. Specifically, glutamate in the nucleus accumbens shows a decreasing logarithmic dose response curve. Finally, regression analysis of 11 published reports employing brain microdialysis experiments in 104 alcohol-dependent rats reveals very consistent augmented extracellular glutamate and GABA levels in various brain sites that correlate with the intensity of the withdrawal response were identified.

Conclusions: In summary, our results provide standardized basal values for future experimental and in silico studies on neurotransmitter release in the rat brain and may be helpful to understand the effect of ethanol on neurotransmitter release. Furthermore, this study illustrates the benefit of meta-analyses using the generalization of a wide range of preclinical data.

No MeSH data available.


Related in: MedlinePlus