ArticleNeurotoxicity research2026
Chronic Administration of Atomoxetine and Methylphenidate Induces Differential Alterations in the Hippocampus and Striatum of Young Rats.
Article in Neurotoxicity research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Atomoxetine (ATX) and methylphenidate (MPH) are routinely prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD). Although the pathophysiology of ADHD is not fully understood, oxidative stress and neuroinflammation have emerged as contributing factors. ATX has been shown to alter several signal transduction pathways and increase oxidative stress, mitochondrial damage, and cell death in vitro and in vivo. Likewise, MPH has been reported to cause DNA damage, oxidative stress, inflammation, and behavioural alterations in vivo. In this study, we aimed to determine whether chronic treatment with ATX and MPH affects neuronal integrity, reactive oxygen species production, and possible neuroinflammatory processes in the hippocampus and striatum of young rats. Wistar rats (postnatal day 23) received intraperitoneal injections of ATX (3 mg/kg) and MPH (10 mg/kg), once a day for 28 consecutive days. Chronic ATX and MPH treatment decreased the number of neurons (cresyl violet staining) in both the hippocampus and striatum. Furthermore, both treatments increased dihydroethidium fluorescent in the hippocampus, indicating elevated superoxide (reactive oxygen species) production. Additionally, the number of glial fibrillary acidic protein-labelled astrocytes was increased in the hippocampus, reflecting a potential neuroinflammation. Taken together, these findings suggest that chronic ATX and MPH administration in young rats produces differential alterations, characterised by neuronal loss in the hippocampus and striatum, alongside increased reactive oxygen species production and a possible neuroinflammation in the hippocampus.
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