{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:11:54Z","timestamp":1789017114945,"version":"build-2803163510"},"reference-count":63,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education and Research","award":["PN-IV-P6-6.1-CoEx-2024-0056"],"award-info":[{"award-number":["PN-IV-P6-6.1-CoEx-2024-0056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Caffeine is a widely consumed psychostimulant that may affect anxiety-like, aggression-like, and social behaviors, potentially in association with oxidative imbalance. Objectives: This study evaluated the behavioral and biochemical effects of acute caffeine exposure in adult zebrafish and investigated the potential protective effects of N-acetylcysteine (NAC). Methods: Sixty adult wild-type AB zebrafish (Danio rerio), approximately 9\u201310 months old, were assigned to six groups (n = 10\/group): control, caffeine (25 or 60 mg\/L), NAC (1 mg\/L), and NAC combined with either caffeine concentration. Behavioral effects were assessed using the Social Preference Test, Mirror-Biting Test, and Novel Tank Test. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured as oxidative stress-related markers. Results: Caffeine increased locomotor activity and induced anxiety-like and aggression-like behavioral alterations, including increased bottom-dwelling, thigmotaxis, and mirror-directed behavior, while reducing social preference. Caffeine significantly increased SOD activity at 25 mg\/L (p = 0.010) and 60 mg\/L (p = 0.008), and GPx activity at 25 mg\/L (p = 0.008) and 60 mg\/L (p = 0.006), compared with controls. NAC attenuated caffeine-induced hyperlocomotion and several anxiety-like and aggression-like alterations and modulated antioxidant enzyme responses, but did not fully restore social preference. Conclusions: Acute caffeine exposure produces behavioral alterations and changes in antioxidant enzyme activity in adult zebrafish. NAC partially attenuates these effects, particularly hyperlocomotion, anxiety-like behavior, and aggression-like responses, while showing more limited effects on caffeine-induced social alterations.<\/jats:p>","DOI":"10.3390\/ph19091419","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:51:48Z","timestamp":1788871908000},"page":"1419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Caffeine-Induced Behavioral Alterations by N-Acetylcysteine in a Pharmacological Challenge Model"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4979-1057","authenticated-orcid":false,"given":"C\u01cet\u01celina","family":"Ionescu","sequence":"first","affiliation":[{"name":"Doctoral School of Biology, Faculty of Biology, \u201cAlexandru Ioan Cuza\u201d University of Ia\u0219i, 700505 Iasi, Romania"},{"name":"\u201cIoan Haulica\u201d Institute, Apollonia University, 700511 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8262-6538","authenticated-orcid":false,"given":"Ramona-Alexandra","family":"Ciau\u015fu","sequence":"additional","affiliation":[{"name":"Doctoral School of Geosciences, Faculty of Geography and Geology, \u201cAlexandru Ioan Cuza\u201d University of Iasi, 700505 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u01celina","family":"Visternicu","sequence":"additional","affiliation":[{"name":"Doctoral School of Biology, Faculty of Biology, \u201cAlexandru Ioan Cuza\u201d University of Ia\u0219i, 700505 Iasi, Romania"},{"name":"\u201cIoan Haulica\u201d Institute, Apollonia University, 700511 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0256-8911","authenticated-orcid":false,"given":"Viorica","family":"Rarinca","sequence":"additional","affiliation":[{"name":"Doctoral School of Biology, Faculty of Biology, \u201cAlexandru Ioan Cuza\u201d University of Ia\u0219i, 700505 Iasi, Romania"},{"name":"\u201cIoan Haulica\u201d Institute, Apollonia University, 700511 Iasi, Romania"},{"name":"Doctoral School of Geosciences, Faculty of Geography and Geology, \u201cAlexandru Ioan Cuza\u201d University of Iasi, 700505 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1194-1768","authenticated-orcid":false,"given":"Gabriel-Ionut","family":"Plavan","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, 700505 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9755-6771","authenticated-orcid":false,"given":"Mircea-Nicusor","family":"Nicoara","sequence":"additional","affiliation":[{"name":"Doctoral School of Geosciences, Faculty of Geography and Geology, \u201cAlexandru Ioan Cuza\u201d University of Iasi, 700505 Iasi, Romania"},{"name":"Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, 700505 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Alin","family":"Ciob\u00eec\u01ce","sequence":"additional","affiliation":[{"name":"\u201cIoan Haulica\u201d Institute, Apollonia University, 700511 Iasi, Romania"},{"name":"Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, 700505 Iasi, Romania"},{"name":"\u201cOlga Necrasov\u201d Center, Department of Biomedical Research, Romanian Academy, 700481 Iasi, Romania"},{"name":"CENEMED Platform for Interdisciplinary Research, University of Medicine and Pharmacy \u201cGrigore T. Popa\u201d, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Luca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6604-874X","authenticated-orcid":false,"given":"Daniel","family":"Timofte","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Ia\u0219i, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otilia","family":"Novac","sequence":"additional","affiliation":[{"name":"Grigore T. 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