Neurochemical mechanisms of alcohol withdrawal

Handb Clin Neurol. 2014:125:133-56. doi: 10.1016/B978-0-444-62619-6.00009-4.


Alcohol dependence encompasses a serious medical and societal problem that constitutes a major public health concern. A serious consequence of dependence is the emergence of symptoms associated with the alcohol withdrawal syndrome when drinking is abruptly terminated or substantially reduced. Clinical features of alcohol withdrawal include signs of central nervous system hyperexcitability, heightened autonomic nervous system activation, and a constellation of symptoms contributing to psychologic discomfort and negative affect. The development of alcohol dependence is a complex and dynamic process that ultimately reflects a maladaptive neurophysiologic state. Perturbations in a wide range of neurochemical systems, including glutamate, γ-aminobutyric acid, monoamines, a host of neuropeptide systems, and various ion channels produced by the chronic presence of alcohol ultimately compromise the functional integrity of the brain. These neuroadaptations not only underlie the emergence and expression of many alcohol withdrawal symptoms, but also contribute to enhanced relapse vulnerability as well as perpetuation of uncontrolled excessive drinking. This chapter highlights the hallmark features of the alcohol withdrawal syndrome, and describes neuroadaptations in a wide array of neurotransmitter and neuromodulator systems (amino acid and monoamine neurotransmitter, neuropeptide systems, and various ion channels) as they relate to the expression of various signs and symptoms of alcohol withdrawal, as well as their relationship to the significant clinical problem of relapse and uncontrolled dangerous drinking.

Keywords: GABA; alcohol dependence; alcohol withdrawal syndrome; glutamate; ion channels; monoamines; neuroadaptations; neurochemical adaptations; neuropeptides.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alcoholism / diagnosis*
  • Alcoholism / metabolism*
  • Animals
  • Biogenic Amines / metabolism
  • Brain / metabolism*
  • Brain / pathology
  • Brain Chemistry / physiology*
  • Glutamic Acid / metabolism
  • Humans
  • Neurotransmitter Agents / metabolism
  • Substance Withdrawal Syndrome / diagnosis*
  • Substance Withdrawal Syndrome / metabolism*


  • Biogenic Amines
  • Neurotransmitter Agents
  • Glutamic Acid