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Objective: The aim of the present study was to investigate NOD-like receptor-3 (NLRP-3)-mediated inflammasome activation in macrophage and microglia cells, which is one of the early step mechanisms in the formation of proinflammatory cytokines, in an autism model and also investigate the possible effect of vortioxetine (VTX), which has a multimodal mechanism of action, in the treatment of autism in a valproic acid (VPA)-induced experimental rat model of autism spectrum disorder (ASD).
Materials and Methods: Male Sprague–Dawley rats were divided into 3 groups: Control (n = 12), ASD (n = 16), and ASD + VTX (n = 16). The VTX (5 mg/kg/day) or saline was administered to the male offspring born from pregnant rats administered VPA (400 mg/kg) or saline, between postnatal 30-45 days. Open field, body splash, and social interaction tests were performed in groups on postnatal days 46-52. The NLRP3 inflammasome components such as NLRP3, caspase-1, and ASC levels were investigated in the prefrontal cortex by real-time polymerase chain reaction. Data were analyzed using 1- or 2-way analysis of variance (ANOVA) and Tukey’s multiple comparison tests, and differences of P < .05 were considered statistically significant.
Results: The ASD model showed increases in locomotor activity and repetitive behaviors like grooming despite decreases in sociability and social interactions. These findings as well as observational malformations supported the formation of an autism model. It was found that sniffing and following behaviors as social interaction markers were significantly increased and avoidance behavior was reduced with VTX treatment. In molecular analyses, NLRP3 inflammasome components, NLRP3, ASC, and caspase-1 were increased in the ASD model. It was observed that VTX treatment statistically significantly reduced the increased NLRP3, caspase-1, and ASC gene expressions in ASD.
Conclusion: In light of the findings of the study, it was thought that the NLRP-3 pathway may have an important role in the neurobiology of ASD. VTX, as a multimodal antidepressant, has some beneficial effects for the improvement of the behavioral and molecular parameters of ASD.
Cite this article as: Arıcıoğlu F, Korkmaz E, Kabacaoğlu G, Bahtiyar B, Sümer E, Yılmaz B. Investigating the effects of vortioxetine in an experimental model of autism spectrum disorder: Role of NOD-like receptor protein-3 inflammasome pathway. Psychiatry Clin Psychopharmacol. Published online December 12, 2026. doi:10.5152/pcp.2025.250018.