article · Behavioral Neuroscience
Social isolation can lead to abnormal aggression, which connects to reduced activity in the anterior cingulate cortex of the brain. An investigation in male mice evaluated how the antiepileptic drug topiramate and direct electrical stimulation influence this brain region and behavioural changes. Isolated mice showed a fifty percent decrease in spontaneous neuronal firing in the anterior cingulate cortex alongside elevated aggression. Systemic administration of topiramate extended the time before an attack, lowered total attack occurrences, enhanced social interaction, and partially restored cortical firing rates by approximately thirty percent. Furthermore, delivering high-frequency electrical stimulation directly to the anterior cingulate cortex achieved comparable outcomes, noticeably decreasing aggressive actions while encouraging sociability. These findings indicate that targeting anterior cingulate cortex hypoactivity through either pharmacological modulation or electrical stimulation can counteract aggression and social deficits.
Excessive aggression and impaired sociability feature prominently across several neuropsychiatric disorders. Demonstrating that dampening aggression is possible through both pharmaceutical treatment and direct brain stimulation provides crucial insight into the underlying brain mechanisms. Pinpointing the anterior cingulate cortex as an operational target helps validate new strategies for managing aggression-related psychiatric conditions that currently have limited treatment options.
The research presents early-stage preclinical findings in animal models that could inform drug development and neuromodulation therapies. Medical device developers and pharmaceutical companies focusing on aggression-related neuropsychiatric conditions could evaluate topiramate derivatives or targeted brain stimulation protocols directed at the anterior cingulate cortex. However, because the study is limited to laboratory rodents, substantial preclinical safety testing and clinical trials remain necessary before therapeutic translation.
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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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DOI: 10.1037/bne0000663
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