en Neurophysiology/Pharmacology Neurophysiology/Pharmacology Experimental research article Experimental research article <span style="font-size:12px;"><span style="font-family:Arial;"><strong>Introduction: </strong>Alzheimer&rsquo;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 (A&beta;) 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 A&beta;.<br /> <strong>Methods: </strong>18 adult Wistar rats were divided into three groups: Saline, A&beta;, and A&beta; + Bufexamac. A&beta;25-35 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.<br /> <strong>Results: </strong>Bufexamac significantly mitigated A&beta;-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 A&beta; 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 A&beta; group.<br /> <strong>Conclusion:</strong> 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.</span></span> Alzheimer’s disease,Bufexamac,Glucocorticoid receptor,Serotonin,Histone deacetylase inhibitors 260 271 http://ppj.phypha.ir/browse.php?a_code=A-10-1618-2&slc_lang=en&sid=1 Monireh Mirehei mirehei.monireh@gmail.com 3200319475328460037978 3200319475328460037978 No Neuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran Fereshteh Motamedi motamedi@ams.ac.ir 3200319475328460037979 3200319475328460037979 No Neuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran Nader Maghsoudi nmaghsoudi@sbmu.ac.ir 3200319475328460037980 3200319475328460037980 No Neuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran Fariba Khodagholi Khodagholi@sbmu.ac.ir 3200319475328460037981 0000000249114530 No Neuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran Fatemeh Abbaszadeh f.abbaszadehm@gmail.com 3200319475328460037982 0000000213743554 Yes Neurobiology Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran