The Highly Selective 5-HT2B Receptor Antagonist MW073 Mitigates Aggressive Behavior in an Alzheimer’s Disease Mouse Model

TL;DR

A drug targeting the 5-HT2B receptor reduces aggressive behavior in a mouse model of Alzheimer's disease.

Contribution

MW073, a selective 5-HT2B receptor antagonist, is shown to mitigate aggression in Alzheimer’s disease mice.

Findings

MW073 significantly reduces the number and duration of aggressive attacks in male Tg2576 mice.

Treatment with MW073 ameliorates aggressive behavior in an Alzheimer’s disease mouse model.

Abstract

What are the main findings?
MW073, a selective 5-HT2B receptor antagonist, significantly reduces both the number and duration of aggressive attacks in male Tg2576 mice.Treatment with MW073 effectively ameliorates aggressive behavior in male Tg2576 mice.

MW073, a selective 5-HT2B receptor antagonist, significantly reduces both the number and duration of aggressive attacks in male Tg2576 mice.

Treatment with MW073 effectively ameliorates aggressive behavior in male Tg2576 mice.

What are the implications of the main findings?
5-HT2B receptor antagonism may represent a targeted therapeutic strategy to reduce pathological aggression.Targeting 5-HT2B receptors could provide a novel approach for managing aggression associated with Alzheimer’s disease–related pathology.

5-HT2B receptor antagonism may represent a targeted therapeutic strategy to reduce pathological aggression.

Targeting 5-HT2B receptors could provide a novel approach for managing aggression associated with Alzheimer’s disease–related pathology.

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and the leading cause of dementia worldwide. Progressive synaptic dysfunction underlies declines in cognition, daily functioning, and the development of neuropsychiatric syndromes. Neuropsychiatric syndromes that include agitation and aggression affect 40–60% of patients and represent a major source of caregiver burden. Serotonin 5-HT2B receptor levels are increased in the AD patient brain, and thus, treatment of AD animal models with the selective 5-HT2B receptor antagonist MW073 in prevention or disease stage paradigms attenuates Aβ- or tau-induced dysfunction. Methods: We investigated the effects of MW073 treatment on the aggressive behavior of Tg2576 mice in a resident–intruder assay. Results: MW073 treatment significantly reduced aggressive behavior in male Tg2576 mice. Conclusions: MW073 efficacy in treating aggression in Tg2576 mice implicates 5-HT2B receptor-mediated signaling in AD neuropsychiatric symptoms as well as cognitive and behavioral dysfunction.

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