Vasopressin and alcohol: a multifaceted relationship

Psychopharmacology (Berl). 2018 Dec;235(12):3363-3379. doi: 10.1007/s00213-018-5099-x. Epub 2018 Nov 3.


Background: Arginine vasopressin (VP) has been implicated in a number of neuropsychiatric disorders with an emphasis on situations where stress increased the severity of the disorder. Based on this hypothesized role for VP in neuropsychiatric disorders, much research is currently being undertaken in humans and animals to test VP as a target for treatment of a number of these disorders including alcohol abuse.

Objectives: To provide a summary of the literature regarding the role of VP in alcohol- and stress-related behaviors including the use of drugs that target VP in clinical trials.

Results: Changes in various components of the VP system occur with alcohol and stress. Manipulating VP or its receptors can alter alcohol- and stress-related behaviors including tolerance to alcohol, alcohol drinking, and anxiety-like behavior. Finally, the hypothalamic-pituitary-adrenal axis response to alcohol is also altered by manipulating the VP system. However, clinical trials of VP antagonists have had mixed results.

Conclusions: A review of VP's involvement in alcohol's actions demonstrates that there is much to be learned about brain regions involved in VP-mediated effects on behavior. Thus, future work should focus on elucidating relevant brain regions. By using previous knowledge of the actions of VP and determining the brain regions and/or systems involved in its different behavioral effects, it may be possible to identify a specific receptor subtype target, drug treatment combination, or specific clinical contexts that may point toward a more successful treatment.

Keywords: Alcohol intake; Amygdala; Antagonists; Anxiety; Clinical trials; Ethanol; Hypothalamus; Stress; Tolerance; Vasopressin.

Publication types

  • Review

MeSH terms

  • Alcohol Drinking / drug therapy
  • Alcohol Drinking / metabolism*
  • Alcohol Drinking / psychology
  • Alcoholism / drug therapy
  • Alcoholism / metabolism*
  • Alcoholism / psychology
  • Animals
  • Antidiuretic Hormone Receptor Antagonists / pharmacology
  • Anxiety / drug therapy
  • Anxiety / metabolism
  • Anxiety / psychology
  • Arginine Vasopressin / antagonists & inhibitors
  • Arginine Vasopressin / metabolism
  • Ethanol / administration & dosage*
  • Ethanol / toxicity
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • Neurophysins / antagonists & inhibitors
  • Neurophysins / metabolism*
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism
  • Protein Precursors / antagonists & inhibitors
  • Protein Precursors / metabolism*
  • Stress, Psychological / drug therapy
  • Stress, Psychological / metabolism
  • Stress, Psychological / psychology
  • Vasopressins / antagonists & inhibitors
  • Vasopressins / metabolism*


  • AVP protein, human
  • Antidiuretic Hormone Receptor Antagonists
  • Neurophysins
  • Protein Precursors
  • Vasopressins
  • Arginine Vasopressin
  • Ethanol