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Cited by 25Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchSubstance Abuse Treatment and Outcomes

The Urge to Fight: Persistent Escalation by Alcohol and Role of NMDA Receptors in Mice

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Covington, Herbert E., Newman, Emily L., Tran, Steven, Walton, Lena, Hayek, Walae, Leonard, Michael Z., DeBold, Joseph F., Miczek, Klaus A.·2018·Frontiers in Behavioral Neuroscience
DOI 10.3389/fnbeh.2018.00206PMC PMC6146040
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Abstract

Alcohol drinking, in some individuals, culminates in pathologically aggressive and violent behaviors. Alcohol can escalate the urge to fight, despite causing disruptions in fighting performance. When orally administered under several dosing conditions the current study examined in a mouse model if repeated alcohol escalates the motivation to fight, the execution of fighting performance, or both. Specifically, seven daily administrations of alcohol (0, 1.8, or 2.2 g/kg) determined if changes in the motivation to initiate aggressive acts occur with, or without, shifts in the severity of fighting behavior. Responding under the control of a fixed interval (FI) schedule for aggression reinforcements across the initial daily sessions indicated the development of tolerance to alcohol's sedative effect. By day 7, alcohol augmented FI response rates for aggression rewards. While alcohol escalated the motivation to fight, fighting performance remained suppressed across the entire 7 days. Augmented FI responding for aggression rewards in response to a low dose of alcohol (1.0 g/kg) proved to be persistent, as we observed sensitized rates of responding for more than a month after alcohol pretreatment. In addition, this sensitization of motivated aggression did not occur with a general enhancement of motor activity. Antagonism of NMDA or AMPA receptors with ketamine, dizocilpine, or NBQX during later challenges with alcohol were largely serenic without having any notable impact on the expression of alcohol-escalated rates of FI responding. The current dissociation of appetitive and performance measures indicates that discrete neural mechanisms controlling aggressive arousal can be distinctly sensitized by alcohol.

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  • Sensitized rates of fixed-interval responding were observed over a month after alcohol pretreatment, indicating that repeated alcohol exposure leads to long-term neuroadaptations that alter future aggressive responses to an alcohol challenge.

    “sensitized rates of FI responding were observed over a month after alcohol pretreatment, indicating that repeated alcohol exposure leads to long term neuroadaptations that alter future aggressive responses to an alcohol challenge.”

    From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Covington et al. 2018

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  • Repeated alcohol administrations via oral gavage at higher doses (1.8-2.2 or 2.4 g/kg) heighten the motivation to engage in a fight, as indicated by increased operant response rates.

    “Covington et al. found that repeated alcohol administrations, via oral gavage, at higher doses (1.8–2.2 or 2.4 g/kg) heightens the motivation to engage in a fight, as indicated by increased operant response rates.”

    From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Covington et al. 2018

    The Methods (Procedures) describe repeated oral doses of 1.8 or 2.2 g/kg, not 2.4 g/kg. The Results (Daily Administrations of Alcohol Dose Dependently Reduced, and Thereafter Escalated, the Motivation to Fight) report that fixed-interval responding for an aggressive reward initially fell, then increased after repeated exposure. Thus the motivation finding is supported, but the 2.4 g/kg dose and the unqualified implication of an increase throughout treatment are not. (LLM, conf=0.90)

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  • Higher doses of alcohol can increase the motivation to fight even when fighting performance is impaired.

    “higher doses of alcohol can increase the motivation to fight, even when fighting performance is impaired (Covington et al. 2018)”

    From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Covington et al. 2018

  • The first administration of a higher dose of alcohol tended to suppress both operant responding and aggressive performance; after repeated administrations, rates of responding increased above baseline while fighting performance remained suppressed.

    “the first administration of a higher dose of alcohol tended to suppress both operant responding and aggressive performance. After repeated administrations, however, rates of responding began to increase above baseline levels, while fighting performance remained suppressed.”

    From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Covington et al. 2018

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Authors
Covington, H. E., Newman, E. L., Tran, S., Walton, L., Hayek, W., Leonard, M. Z., DeBold, J. F., & Miczek, K. A.
Affiliations
Tufts University (US)
Corresponding author
  • Covington, Herbert E.
  • Miczek, Klaus A.
ORCID
Venue
Frontiers in Behavioral Neuroscience
Publisher
Frontiers Media SA
Published
2018-09-13
Volume
12
Pages
206-206
ISSN
1662-5153 (ISSN-L)
DOI
10.3389/fnbeh.2018.00206
PMC
PMC6146040
OpenAlex
W2890800308
Cited by
25
References
2
Citations by year
2025: 2 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 1
FWCI
1.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Institute on Alcohol Abuse and Alcoholism (AA013983, AA025827)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
alcohol, aggression, fighting behavior, NMDA receptor, AMPA receptors, alcohol tolerance, fixed-interval schedules, ketamine, MK-801, NBQX

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