Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul;240(7):1473-1492.
doi: 10.1007/s00213-023-06381-z. Epub 2023 May 23.

Effects of topiramate on morphological and structural alterations of the anterior cingulate cortex in aggressive socially isolated mice

Ilias Chaibi  1 , Ihsane Ait-Mansour  1 , Mohamed Tari  1 , Mohamed Bennis  2 , Saadia Ba-M'hamed  1
Affiliations

Effects of topiramate on morphological and structural alterations of the anterior cingulate cortex in aggressive socially isolated mice

Ilias Chaibi et al. Psychopharmacology (Berl). 2023 Jul.

Abstract

Rationale: Topiramate, an approved antiepileptic drug, was found effective in treating aggressive symptoms in humans and rodents. However, the effects and mechanisms of Topiramate on aggressive behavior are still unclear. Our previous study indicated that intraperitoneal administration of Topiramate successfully decreased aggression and reinforced sociability in socially aggressive mice, and increased cFos-expressing neurons in the anterior cingulate cortex (ACC). In addition to its pharmacological properties, previous studies have approved the neuroprotective effects of Topiramate. These suggest a potential effect of Topiramate on ACC's structure and function.

Objectives and results: In the present study, we first investigated the structural characteristics of ACC in the social isolation-induced aggression paradigm. The results showed that hyper-aggressive behavior in socially aggressive mice was associated with several structural alterations in ACC: increased neuron death combined with decreased neuron density, increased damaged neuronal morphology and increased neuroinflammation markers. Based on these observations, we next investigated the potential neuroprotective effect of Topiramate against structural alterations of ACC observed in socially aggressive mice. Results indicated that intraperitoneal administration of Topiramate (30 mg/kg) decreased aggression and enhanced sociability without affecting locomotor activity. Interestingly, the anti-aggressive effect of Topiramate was associated with decreased neuronal death, ameliorated damaged neuronal morphology, and decreased reactive microglia markers in ACC.

Conclusions: Our results provide insights into the structural alterations of ACC in aggressive socially aggressive mice. Moreover, the present study suggested that the anti-aggressive effect of Topiramate could be related to its neuroprotective effects against the structural alterations of ACC.

Keywords: Aggression; Anterior cingulate cortex; Neuroinflammation; Social isolation; Topiramate.

PubMed Disclaimer

References

    1. Blair RJR (2013) The neurobiology of psychopathic traits in youths. Nat Rev Neurosci 14:786–799. https://doi.org/10.1038/nrn3577 - DOI - PubMed - PMC
    1. Bouchatta O, Chaibi I, Baba AA et al (2020) The effects of Topiramate on isolation-induced aggression: a behavioral and immunohistochemical study in mice. Psychopharmacology (Berl) 237(8):2451–2467. https://doi.org/10.1007/s00213-020-05546-4
    1. Chaibi I, Bouchatta O, Bennis M, Ba-M’hamed S (2020) Bidirectional effects of Topiramate on anterior cingulate cortex region related aggressive behavior. Neurosci Lett 737:135307. https://doi.org/10.1016/j.neulet.2020.135307 - DOI - PubMed
    1. Chaibi I, Bennis M, Ba-M’Hamed S (2021) GABA-A receptor signaling in the anterior cingulate cortex modulates aggression and anxiety-related behaviors in socially aggressive mice. Brain Res 1762:147440. https://doi.org/10.1016/j.brainres.2021.147440 - DOI - PubMed
    1. Chaibi I, Bouchatta O, Bennis M, Ba-M’hamed S (2023) The role of the anterior cingulate cortex in aggression and impulsivity. Behav Neurosci. https://doi.org/10.1037/bne0000552.Advanceonlinepublication.10.1037/bne0... - DOI - PubMed