{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T02:04:01Z","timestamp":1784167441958,"version":"3.55.0"},"reference-count":64,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Ciprofloxacin (CPX) has been associated with neuropsychiatric adverse effects; however, its contribution to depression-like behaviors and the underlying neurobiological mechanisms remain insufficiently characterized. Previous studies have indicated that cinnamic acid (CA) may exert protective actions in the nervous system by modulating oxidative and inflammatory pathways. Nevertheless, its effectiveness in preventing CPX-induced neurobehavioral impairments remains largely unknown. The present study aimed to investigate whether CA attenuates CPX-induced depression-like behaviors through modulation of neuroinflammation and oxidative stress. This study included 60 male Swiss albino mice distributed among six experimental groups (n = 10). Animals were assigned to receive a vehicle, CPX administered at 80 mg\/kg, CPX combined with CA at doses of 50, 100, or 200 mg\/kg, or CPX together with FLX (20 mg\/kg) throughout the 14-day treatment period. Behavioral alterations were assessed using social interaction, forced swimming, tail suspension, and sucrose preference paradigms. In addition, hippocampal and prefrontal cortex tissues were examined for oxidative stress markers (MDA, GSH, and CAT), pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, and IL-6), and neurotransmitters (serotonin, dopamine, and GABA) using ELISA-based assays. CPX administration induced significant depression-like behaviors, evidenced by reduced social interaction, increased immobility, and anhedonia (p &lt; 0.05). These behavioral alterations were associated with increased lipid peroxidation, impaired antioxidant defense, elevated pro-inflammatory cytokine levels, and decreased monoaminergic and GABAergic neurotransmission in both HIP and PFC regions. CA treatment significantly improved CPX-induced behavioral and neurochemical alterations. Among the tested doses, the 100 mg\/kg regimen produced the most consistent response, accompanied by reduced neuroinflammatory activity and restoration of neurotransmitter levels, particularly in the hippocampus. In conclusion, CA mitigated CPX-induced behavioral deficits and neurochemical alterations, an effect that may be attributed to its regulatory influence on oxidative stress, neuroinflammatory processes, and neurotransmitter balance within the HIP\u2013PFC pathway. Collectively, the findings indicate that CA may have therapeutic relevance in reducing the neuropsychiatric consequences associated with CPX exposure.<\/jats:p>","DOI":"10.3390\/biology15141156","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:05:07Z","timestamp":1784163907000},"page":"1156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cinnamic Acid Attenuates Ciprofloxacin-Induced Depression-like Behavior via Modulation of Neuroinflammation, Oxidative Stress, and Neurotransmitter Homeostasis in the Hippocampus\u2013Prefrontal Cortex Axis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0334-8152","authenticated-orcid":false,"given":"Ares","family":"Alizade","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, Van Y\u00fcz\u00fcnc\u00fc Y\u0131l University, 65080 Van, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2246-4550","authenticated-orcid":false,"given":"Nur","family":"Akman","sequence":"additional","affiliation":[{"name":"Department of Midwifery, Faculty of Health Sciences, Van Y\u00fcz\u00fcnc\u00fc Y\u0131l University, 65080 Van, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1080\/08923973.2021.1905658","article-title":"Neuroprotective role of camphor against ciprofloxacin induced depression in rats: Modulation of Nrf-2 and TLR4","volume":"43","author":"Salama","year":"2021","journal-title":"Immunopharmacol. 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