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Cited by 12Substance Abuse Treatment and OutcomesNeurotransmitter Receptor Influence on BehaviorAlcohol Consumption and Health Effects

Noradrenergic Mechanisms and Circuitry of Hyperkatifeia in Alcohol Use Disorder

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Varodayan, Florence P., Erikson, Chloe M., Scroger, Marcis V., Roberto, Marisa·2025·Biological Psychiatry
DOI 10.1016/j.biopsych.2024.09.009PMC PMC11839382
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Abstract

Hyperkatifeia, the manifestation of emotional distress or pain, is a conceptual framework gaining traction throughout the alcohol and other substance use fields as an important driver of addiction. It is well known that previous or current negative life experiences can serve as powerful motivators for excessive alcohol consumption and precipitate the development of an alcohol use disorder (AUD). A major hallmark of later stages of AUD is the emergence of hyperkatifeia during withdrawal, which can persist well into protracted abstinence to drive relapse. Given these complex interactions, understanding the specific neuroadaptations that lie at the intersection of hyperkatifeia and AUD can inform ongoing therapeutic development. The monoamine norepinephrine is of particular interest. Noradrenergic dysfunction is implicated in AUD, anxiety, chronic stress, depression, and emotional and physical pain. Importantly, there are key sexual dimorphisms within the noradrenergic system that are thought to differentially impact the development and trajectory of AUD in women and men. In the current review, we discuss past and recent work on noradrenergic influences at each stage of the AUD cycle (binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation) through the lens of hyperkatifeia. Evidence from these studies support the prioritization of norepinephrine-specific drug development to treat AUD and the identification of AUD subpopulations that may benefit the most from these therapies (e.g., women or people with comorbid chronic pain or anxiety/stress disorders).

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Cited by

Sorted by citations

Authors
Varodayan, F. P., Erikson, C. M., Scroger, M. V., & Roberto, M.
Affiliations
  • Binghamton University (US)
  • Scripps Research Institute (US)
Corresponding author
  • Varodayan, Florence P.
  • Roberto, Marisa
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2025-03
Volume
97
Issue
6
Pages
580-589
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2024.09.009
PMC
PMC11839382
OpenAlex
W4402632748
Cited by
12
References
7
Citations by year
2026: 7 · 2025: 5
FWCI
0.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Alcohol Abuse and Alcoholism (AA031101, AA021491, AA017823, AA013498, AA017447, P60 AA006420, T32 AA007456, AA025408, AA029841, AA027700)
  • US Government National Institutes of Health
Topics
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords
alcoholism, norepinephrine, noradrenergic dysfunction, alcohol withdrawal, relapse, sexual dimorphism, chronic pain, anxiety, chronic stress
MeSH terms
Alcoholism, Animals, Brain, Humans, Norepinephrine, Substance Withdrawal Syndrome

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