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Topiramate and anterior cingulate cortex high-frequency stimulation mitigate aggression and promote sociability in socially isolated male mice.

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Τίτλος: Topiramate and anterior cingulate cortex high-frequency stimulation mitigate aggression and promote sociability in socially isolated male mice.
Συγγραφείς: Chaibi I; Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences, Cadi Ayyad University., Lamghari Moubarrad FZ; Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences, Cadi Ayyad University., Bennis M; Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences, Cadi Ayyad University., Ba-M'hamed S; Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences, Cadi Ayyad University.
Πηγή: Behavioral neuroscience [Behav Neurosci] 2026 Oct; Vol. 140 (5), pp. 327-338. Date of Electronic Publication: 2026 Aug 10.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: American Psychological Association Country of Publication: United States NLM ID: 8302411 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-0084 (Electronic) Linking ISSN: 07357044 NLM ISO Abbreviation: Behav Neurosci Subsets: MEDLINE
Imprint Name(s): Original Publication: Washington, D.C. : American Psychological Association, [c1983-
Ιατρικοί όροι (MeSH): Topiramate*/pharmacology , Aggression*/drug effects , Aggression*/physiology , Gyrus Cinguli*/drug effects , Gyrus Cinguli*/physiology , Social Isolation*/psychology, Neurons/drug effects ; Neurons/physiology ; Behavior, Animal/drug effects ; Anticonvulsants/pharmacology ; Electric Stimulation/methods ; Animals ; Male ; Mice ; Social Behavior ; Mice, Inbred C57BL
Περίληψη: Excessive aggression induced by social isolation (SI) has been closely linked to dysfunction in prefrontal circuits, particularly the anterior cingulate cortex (ACC). Topiramate, an antiepileptic drug known to enhance GABAergic and inhibit glutamatergic transmission, has demonstrated antiaggressive effects. In our previous work, we showed that topiramate's antiaggressive effects were associated with reduced neuronal death, improved neuronal morphology, and attenuated neuroinflammation in the ACC following SI. However, its impact on ACC neuronal activity remains poorly understood. In this study, we investigated the effects of topiramate on the spontaneous activity of ACC neurons in a mouse model of SI-induced aggression. Additionally, we explored whether direct restoration of ACC activity via high-frequency stimulation could similarly reduce excessive aggression. Systemic administration of topiramate (30 mg/kg, intraperitoneally) significantly increased attack latency, reduced attack frequency, and enhanced sociability. In vivo extracellular recording of spontaneous activity revealed a 50% reduction in ACC firing in isolated mice, which was partially restored (∼30%) by topiramate treatment. Moreover, high-frequency stimulation applied to the ACC markedly decreased aggressive behavior and robustly promoted social interaction. Together, these results provide convergent behavioral and electrophysiological evidence that SI-induced aggression is associated with ACC hypoactivity. The finding that both topiramate treatment and high-frequency stimulation of the ACC effectively reversed these deficits highlights the ACC as a key target for therapeutic interventions to treat aggression-related neuropsychiatric conditions. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Substance Nomenclature: 0H73WJJ391 (Topiramate)
0 (Anticonvulsants)
Entry Date(s): Date Created: 20260810 Date Completed: 20260924 Latest Revision: 20260924
Update Code: 20260925
DOI: 10.1037/bne0000663
PMID: 42574119
Βάση Δεδομένων: MEDLINE
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  Data: Topiramate and anterior cingulate cortex high-frequency stimulation mitigate aggression and promote sociability in socially isolated male mice.
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  Data: <searchLink fieldCode="AU" term="%22Chaibi+I%22">Chaibi I</searchLink>; Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences, Cadi Ayyad University.<br /><searchLink fieldCode="AU" term="%22Lamghari+Moubarrad+FZ%22">Lamghari Moubarrad FZ</searchLink>; Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences, Cadi Ayyad University.<br /><searchLink fieldCode="AU" term="%22Bennis+M%22">Bennis M</searchLink>; Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences, Cadi Ayyad University.<br /><searchLink fieldCode="AU" term="%22Ba-M'hamed+S%22">Ba-M'hamed S</searchLink>; Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences, Cadi Ayyad University.
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  Data: <searchLink fieldCode="JN" term="%228302411%22">Behavioral neuroscience</searchLink> [Behav Neurosci] 2026 Oct; Vol. 140 (5), pp. 327-338. <i>Date of Electronic Publication: </i>2026 Aug 10.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22American+Psychological+Association%22">American Psychological Association </searchLink><i>Country of Publication: </i>United States <i>NLM ID: </i>8302411 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1939-0084 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2207357044%22">07357044 </searchLink><i>NLM ISO Abbreviation: </i>Behav Neurosci <i>Subsets: </i>MEDLINE
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  Data: <i>Original Publication</i>: Washington, D.C. : American Psychological Association, [c1983-
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  Data: <searchLink fieldCode="MM" term="%22Topiramate%22">Topiramate*</searchLink>/<searchLink fieldCode="MM" term="%22Topiramate+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Aggression%22">Aggression*</searchLink>/<searchLink fieldCode="MM" term="%22Aggression+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Aggression%22">Aggression*</searchLink>/<searchLink fieldCode="MM" term="%22Aggression+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Gyrus+Cinguli%22">Gyrus Cinguli*</searchLink>/<searchLink fieldCode="MM" term="%22Gyrus+Cinguli+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Gyrus+Cinguli%22">Gyrus Cinguli*</searchLink>/<searchLink fieldCode="MM" term="%22Gyrus+Cinguli+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Social+Isolation%22">Social Isolation*</searchLink>/<searchLink fieldCode="MM" term="%22Social+Isolation+psychology%22">psychology</searchLink><br /><searchLink fieldCode="MH" term="%22Neurons%22">Neurons</searchLink>/<searchLink fieldCode="MH" term="%22Neurons+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Neurons%22">Neurons</searchLink>/<searchLink fieldCode="MH" term="%22Neurons+physiology%22">physiology</searchLink> ; <searchLink fieldCode="MH" term="%22Behavior%2C+Animal%22">Behavior, Animal</searchLink>/<searchLink fieldCode="MH" term="%22Behavior%2C+Animal+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Anticonvulsants%22">Anticonvulsants</searchLink>/<searchLink fieldCode="MH" term="%22Anticonvulsants+pharmacology%22">pharmacology</searchLink> ; <searchLink fieldCode="MH" term="%22Electric+Stimulation%22">Electric Stimulation</searchLink>/<searchLink fieldCode="MH" term="%22Electric+Stimulation+methods%22">methods</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink> ; <searchLink fieldCode="MH" term="%22Social+Behavior%22">Social Behavior</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%2C+Inbred+C57BL%22">Mice, Inbred C57BL</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Excessive aggression induced by social isolation (SI) has been closely linked to dysfunction in prefrontal circuits, particularly the anterior cingulate cortex (ACC). Topiramate, an antiepileptic drug known to enhance GABAergic and inhibit glutamatergic transmission, has demonstrated antiaggressive effects. In our previous work, we showed that topiramate's antiaggressive effects were associated with reduced neuronal death, improved neuronal morphology, and attenuated neuroinflammation in the ACC following SI. However, its impact on ACC neuronal activity remains poorly understood. In this study, we investigated the effects of topiramate on the spontaneous activity of ACC neurons in a mouse model of SI-induced aggression. Additionally, we explored whether direct restoration of ACC activity via high-frequency stimulation could similarly reduce excessive aggression. Systemic administration of topiramate (30 mg/kg, intraperitoneally) significantly increased attack latency, reduced attack frequency, and enhanced sociability. In vivo extracellular recording of spontaneous activity revealed a 50% reduction in ACC firing in isolated mice, which was partially restored (∼30%) by topiramate treatment. Moreover, high-frequency stimulation applied to the ACC markedly decreased aggressive behavior and robustly promoted social interaction. Together, these results provide convergent behavioral and electrophysiological evidence that SI-induced aggression is associated with ACC hypoactivity. The finding that both topiramate treatment and high-frequency stimulation of the ACC effectively reversed these deficits highlights the ACC as a key target for therapeutic interventions to treat aggression-related neuropsychiatric conditions. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
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  Data: 0H73WJJ391 (Topiramate)<br />0 (Anticonvulsants)
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  Data: <i>Date Created: </i>20260810 <i>Date Completed: </i>20260924 <i>Latest Revision: </i>20260924
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  Data: 10.1037/bne0000663
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  Data: 42574119
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42574119
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1037/bne0000663
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 327
    Subjects:
      – SubjectFull: Neurons drug effects
        Type: general
      – SubjectFull: Neurons physiology
        Type: general
      – SubjectFull: Behavior, Animal drug effects
        Type: general
      – SubjectFull: Anticonvulsants pharmacology
        Type: general
      – SubjectFull: Electric Stimulation methods
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Male
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Social Behavior
        Type: general
      – SubjectFull: Mice, Inbred C57BL
        Type: general
      – SubjectFull: Topiramate pharmacology
        Type: general
      – SubjectFull: Aggression drug effects
        Type: general
      – SubjectFull: Aggression physiology
        Type: general
      – SubjectFull: Gyrus Cinguli drug effects
        Type: general
      – SubjectFull: Gyrus Cinguli physiology
        Type: general
      – SubjectFull: Social Isolation psychology
        Type: general
    Titles:
      – TitleFull: Topiramate and anterior cingulate cortex high-frequency stimulation mitigate aggression and promote sociability in socially isolated male mice.
        Type: main
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            NameFull: Chaibi I
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            NameFull: Lamghari Moubarrad FZ
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            – D: 01
              M: 10
              Text: 2026 Oct
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1939-0084
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              Value: 140
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              Value: 5
          Titles:
            – TitleFull: Behavioral neuroscience
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