the role of bufexamac in reducing anxiety levels: focus on hpa axis dysfunction and neurotransmitter regulation in a rat model of alzheimer’s disease

Introduction: alzheimer’s disease (ad) is a neurocognitive disorder characterized by neuropsychiatric symptoms (nps), particularly anxiety. the underlying mechanisms involve disruptions in the hypothalamic-pituitary-adrenal (hpa) axis, and altered serotonergic signaling due to amyloid-beta (aβ) accumu-lation. this study investigates the effects of bufexamac, a cyclooxygenase-2 (cox-2), and hdac class iib inhibitor, on anxiety-like behaviors and neurochemical changes in a rat model of ad induced by aβ.methods: 18 adult wistar rats were divided into three groups: saline, aβ, and aβ + bufexamac. aβ25-35 was administered via intracerebroventricular injection, followed by daily bufexamac treatment for eight days. anxiety-like behaviors were assessed using the open-field test, while western blotting and elisa measured levels of glucocorticoid receptors (gr), corticotropin releasing factor (crf), and serotonin in the amygdala.results: bufexamac significantly mitigated aβ-induced anxiety-like behaviors, as evidenced by increased line crossings and time spent in the center of the arena (p<0.05). western blot analysis revealed that bufexamac reduced elevated gr levels in the aβ group (p<0.05). additionally, bufexamac treat-ment significantly regulated serotonin (p<0.01) and crf levels (p<0.05) in the amygdala compared to the aβ group.conclusion: bufexamac effectively alleviates anxiety-like behaviors and restores neurochemical alterations in a rat model of ad, suggesting its potential as a possible therapeutic agent targeting neuropsychiatric symptoms associated with ad. further research is warranted to explore its clinical applicability.