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Vasopressin and alcohol: a multifaceted relationship

Abstract

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.

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Fig. 1

Abbreviations

AA:

alcohol-preferring

ACTH:

adrenocorticotropic hormone

AMY:

amygdala

ANA:

alcohol non-preferring

AUD:

alcohol use disorder

BST:

bed nucleus of the stria terminalis

cAMP:

cyclic adenosine 3′,5′-monophosphate

CeA:

central nucleus of the amygdala

CORT:

corticosterone

CRF:

corticotropin- releasing factor

CRF-R1:

corticotropin-releasing factor receptor 1

CRF-R2:

corticotropin-releasing factor receptor 2

DGAVP:

des-Gly9-[Arg8]-vasopressin dicitrate

DMH:

dorsomedial hypothalamic nucleus

DR:

dorsal raphe

DSM-5:

Diagnostic and Statistical Manual of Mental Disorders, 5th Edition

GABA:

gamma-aminobutyric acid

HAD:

high alcohol-drinking

HPA:

hypothalamic–pituitary–adrenal

HPC:

hippocampus

LBH:

lateral habenular nucleus

LC:

locus coeruleus

LS:

lateral septum

MeA:

medial amygdala

MPO AH:

medial preoptic area–anterior hypothalamus

mRNA:

messanger RNA

OT:

oxytocin

*OT:

olfactory tubercle

P:

alcohol-preferring

PAG:

periaqueductal gray

PIP2:

phosphatidylinositol 4,5-bisphosphate

POMS:

profile of mood states

PV:

periventricular nucleus hypothalamus

PVN:

paraventricular nucleus

SCN:

suprachiasmatic nucleus

SON:

supraoptic nucleus

STAI:

Spielberger trait anxiety index

V1a:

vasopressin 1a receptor

V1b:

vasopressin 1b receptor

V2:

vasopressin 2 receptor

VOLT:

vascular organ of the lamina terminalis

VP:

arginine vasopressin

*VP:

ventral pallidum

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Acknowledgments

The authors would like to thank Dr. Fulton Crews for his comments on this manuscript.

Funding

This work was supported in part by the Bowles Center for Alcohol Studies and the National Institute on Alcoholism and Alcohol Abuse (P60AA01165; R01AA022234; R01AA021275).

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Correspondence to Kathryn M. Harper.

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Harper, K.M., Knapp, D.J., Criswell, H.E. et al. Vasopressin and alcohol: a multifaceted relationship. Psychopharmacology 235, 3363–3379 (2018). https://doi.org/10.1007/s00213-018-5099-x

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Keywords

  • Ethanol
  • Vasopressin
  • Hypothalamus
  • Amygdala
  • Anxiety
  • Alcohol intake
  • Tolerance
  • Clinical trials
  • Antagonists
  • Stress