{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:08:48Z","timestamp":1778742528798,"version":"3.51.4"},"reference-count":92,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tramadol (TM) abuse results in significant cognitive dysfunction. This study aimed to investigate the impact of an 8\u2010week high\u2010intensity interval training (HIIT) regimen and methylphenidate (MPH) administration (alone and in combination) on cognitive function and hippocampal oxidative stress markers following chronic TM administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Fifty\u2010six adult male rats (200\u2013250\u00a0g) were divided into eight groups and received one of the following treatments: tramadol (50\u00a0mg\/kg, intraperitoneally, 5 days\/week for the first month and 3 days\/week for the second month), methylphenidate (10\u00a0mg\/kg, intraperitoneally, 3 times\/week for 60 days), HIIT (five sessions\/week for 8 weeks), or saline (1\u00a0mL, intraperitoneally, daily for 60 days). Learning and memory were assessed using the Morris water maze (MWM) and passive avoidance tests. Hippocampal malondialdehyde (MDA), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) were measured using TBARS and FRAP methods, respectively. Hippocampal nitric oxide (NO) levels were determined with a commercial assay kit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tramadol induced significant impairments in learning and memory (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). MPH, HIIT, and their combination attenuated these deficits. Tramadol and MPH increased MDA and NO levels (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001) and reduced TAC (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). In contrast, HIIT reduced these parameters, even in the presence of MPH. In fact, HIIT reversed the adverse effects of tramadol and MPH by reducing MDA and NO (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001) and by increasing GPx (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05) and TAC (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although both MPH and HIIT interventions show promise in mitigating tramadol\u2010induced cognitive deficits, their mechanisms of action appear to differ significantly. HIIT likely exerts its effects by modulating oxidative stress, whereas MPH seems to disrupt it, suggesting distinct underlying mechanisms. Further studies are required to elucidate these mechanisms in greater detail.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70925","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T12:35:09Z","timestamp":1758976509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ameliorative Effects of High\u2010Intensity Interval Training (HIIT) and Methylphenidate Against Tramadol\u2010Induced Cognitive Impairment: The Role of Hippocampal Oxidative Stress"],"prefix":"10.1002","volume":"15","author":[{"given":"Sara","family":"Shirazpour","sequence":"first","affiliation":[{"name":"Physiology Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences  Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farahnaz","family":"Taheri","sequence":"additional","affiliation":[{"name":"Neurology Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences  Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gholamreza","family":"Sepehri","sequence":"additional","affiliation":[{"name":"Physiology Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences  Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manzumeh Shamsi","family":"Meymandi","sequence":"additional","affiliation":[{"name":"Physiology Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences  Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahla","family":"Zangiabadizadeh","sequence":"additional","affiliation":[{"name":"Physiology Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences  Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mostafa","family":"Zangiabadi","sequence":"additional","affiliation":[{"name":"Veterinary Medicine Student, School of Veterinary Medicine Shahid Bahonar University of Kerman  Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najmeh Sadat","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Bone Vascular and Microcirculation Laboratory, Department of Kinesiology University of Texas at Arlington  Arlington Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Amin","family":"Rajizadeh","sequence":"additional","affiliation":[{"name":"Physiology Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences  Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Sheikhi","sequence":"additional","affiliation":[{"name":"Veterinary Medicine Student, School of Veterinary Medicine Shahid Bahonar University of Kerman  Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazanin","family":"Sabet","sequence":"additional","affiliation":[{"name":"Physiology Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences  Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2017.11.013"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.26873\/SVR-677-2018"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.33263\/BRIAC106.72097222"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2013.07.018"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-021-05903-x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-018-0194-6"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1996.0292"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.04.022"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-014-0976-5"},{"issue":"01","key":"e_1_2_11_11_1","first-page":"21","article-title":"Lifelong Voluntary Exercise Modulates Age\u2010Related Changes in Oxidative Stress","volume":"40","author":"Bouzid M. 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