title: A heuristic model of alcohol dependence.
abstract: BACKGROUND
  Substance dependence poses a critical health problem. Sadly, its neurobiological mechanisms are still unclear, and this lack of real understanding is reflected in insufficient treatment options. It has been hypothesized that alcohol effects are due to an imbalance between neuroexcitatory and neuroinhibitory amino acids. However, glutamate and GABA interact with other neurotransmitters, which form a complicated network whose functioning evades intuition and should be investigated systemically with methods of biomedical systems analysis.
  
  
  RESULTS
  We present a heuristic model of neurotransmitters that combines a neurochemical interaction matrix at the biochemical level with a mobile describing the balances between pairs of neurotransmitters at the physiological and behavioral level. We investigate the effects of alcohol on the integrated neurotransmitter systems at both levels. The model simulation results are consistent with clinical and experimental observations. The model demonstrates that the drug diazepam for symptoms of alcohol withdrawal effectively reduces the imbalances between neurotransmitters. Moreover, the acetylcholine signal is suggested as a novel target for treatment of symptoms associated with alcohol withdrawal.
  
  
  CONCLUSIONS
  Efficient means of integrating clinical symptoms across multiple levels are still scarce and difficult to establish. We present a heuristic model of systemic neurotransmitter functionality that permits the assessment of genetic, biochemical, and pharmacological perturbations. The model can serve as a tool to represent clinical and biological observations and explore various scenarios associated with alcohol dependence and its treatments. It also is very well suited for educational purposes.
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University Medical School, Atlanta, Georgia, United States of America; Integrative BioSystems Institute, Georgia Institute of Technology, Atlanta, Georgia, United States of America; Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Isar-Amper-Klinikum gemeinnützige GmbH, Klinikum München-Ost, Haar, Landkreis München, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Tretter
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University Medical School, Atlanta, Georgia, United States of America; Integrative BioSystems Institute, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors.forename: Eberhard O
authors.initials: EO
authors.lastname: Voit
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology; D003975:Diazepam / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008960:Models, Psychological; D018377:Neurotransmitter Agents / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D003975:Diazepam