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Cited by 52Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeuroendocrine regulation and behavior

GABAA receptors in the dorsal raphé nucleus of mice: escalation of aggression after alcohol consumption

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Takahashi, Aki, Kwa, Carolyn, DeBold, Joseph F., Miczek, Klaus A.·2010·Psychopharmacology
DOI 10.1007/s00213-010-1920-xPMC PMC2992972
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Abstract

Rationale The dorsal raphé nucleus (DRN), the origin for serotonin (5-HT) in forebrain areas, has been implicated in the neural control of escalated aggression. Gamma aminobutyric acid type-A (GABA(A)) and type-B (GABA(B)) receptors are expressed in the DRN and modulate 5-HT neuronal activity, and both play a role in the behavioral effect of alcohol. Objective The purpose of this study is to examine the interaction between drugs acting on GABA receptors in the DRN and alcohol in their effects on aggressive behaviors. Method Male CFW mice, housed with a female, were trained to self-administer ethanol (1.0 g/kg) or water via an operant conditioning panel in their home cage. Immediately after they drank either ethanol or water, the animals were microinfused with a GABAergic drug into the DRN, and their aggressive behaviors were assessed 10 min later. Muscimol (0.006 nmol), a GABA(A) receptor agonist, escalated alcohol-heightened aggression but had no effect in the absence of ethanol. This effect of muscimol was prominent in the animals that showed alcohol-heightened aggression, but not the animals that reduced or did not change aggressive behavior after ethanol infusion compared to water. On the other hand, the GABA(B) agonist baclofen (0.06 nmol) increased aggressive behavior similarly in both water and ethanol conditions. Antagonists of the GABA(A) and GABA(B) receptors, bicuculline (0.006 nmol) and phaclofen (0.3 nmol) respectively, did not suppress heightened-aggressive behavior induced by ethanol self-administration. Conclusion GABA(A) receptors in the DRN are one of the neurobiological targets of alcohol-heightened aggression. Activation of the GABA(B) receptors in the DRN also produced escalated aggression, but that is independent of the effect of alcohol.

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  • Susceptibility to alcohol's aggression-heightening effects is linked with neural mechanisms including changes in serotonin 5-HT1B signaling, GABAergic signaling, and glutamatergic systems.

    “The susceptibility to alcohol’s aggression-heightening effects has been linked with several neural mechanisms (Miczek et al. 2002), including changes in serotonin signaling, particularly in the 5-HT1B system (Fish et al. 1999; Faccidomo et al. 2008), as well as changes in GABAergic signaling (Takahashi et al. 2010) and glutamatergic systems (Newman et al. 2012, 2018; Covington et al. 2018).”

    From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Takahashi et al. 2010

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Authors
Takahashi, A., Kwa, C., DeBold, J. F., & Miczek, K. A.
Affiliations
Tufts University (US)
Corresponding author
Miczek, Klaus A.
ORCID
Venue
Psychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2010-06-30
Volume
211
Issue
4
Pages
467-477
ISSN
  • 0033-3158 (ISSN-L)
  • 1432-2072
DOI
10.1007/s00213-010-1920-x
PMC
PMC2992972
OpenAlex
W1989051530
Cited by
52
References
1
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 3 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 5 · 2013: 5 · 2012: 8
FWCI
2.20
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Psychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Heart Association
  • National Institute on Alcohol Abuse and Alcoholism (AA13983, R01AA013983)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords
GABAA receptor, GABAB receptors, dorsal raphe nucleus, alcohol, ethanol self-administration, muscimol, baclofen, bicuculline, phaclofen, serotonin
MeSH terms
Aggression, Ethanol, Animals, Baclofen, Behavior, Animal, Bicuculline, Male, Muscimol, Raphe Nuclei, Receptors, GABA-A, Self Administration, Receptors, GABA-B, GABA Agonists, GABA Antagonists, Mice

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