{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T14:42:39Z","timestamp":1793457759517,"version":"4.5.0"},"reference-count":74,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["88887.648941\/2021-00"],"award-info":[{"award-number":["88887.648941\/2021-00"]}]},{"name":"CAPES\/PROEX","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"CAPES\/PROEX","award":["88887.648941\/2021-00"],"award-info":[{"award-number":["88887.648941\/2021-00"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["88887.648941\/2021-00"],"award-info":[{"award-number":["88887.648941\/2021-00"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio Grande do Sul (FAPERGS)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio Grande do Sul (FAPERGS)","award":["88887.648941\/2021-00"],"award-info":[{"award-number":["88887.648941\/2021-00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Major depressive disorder (MDD) is a debilitating illness, and chronic stress is a contributing factor for depressive symptoms. However, despite intense research, the mechanisms of MDD remain substantially unidentified. Quercetin is a powerful flavonoid and could be used as a possible therapeutic strategy for depression. Acknowledging the potential benefits of quercetin, this study investigated its effect alone or in association with the standard drug tranylcypromine (TCP) in a rodent model of chronic restraint stress (CRS). Methods: Adult male rats were subjected to a CRS model consisting of an immobilization session of 4 h daily during 14 consecutive days. Quercetin (50 mg\/kg, gavage) was administered for 45 days. TCP (10 mg\/kg, gavage) was administered for 14 days. Behavioral tasks were conducted to assess locomotor functions, memory, anhedonia, depression-like behaviors, and anxiety-like behaviors. The activity, gene expression, and protein density of acetylcholinesterase (AChE) were investigated. Results: Behavioral tasks showed that the CRS model effectively induced stable behavioral changes. CRS did not alter locomotor function assessed by the open field test (OFT) or anhedonia behavior assessed by the sucrose preference test (SPT). CRS increased total fecal count, which was prevented by quercetin administration in rats. TCP and the association of quercetin and TCP increased the recognition index in comparison with the CRS group in the novel object recognition (NOR) test and improved the swimming and immobility times in comparison to stressed animals in the forced swim test (FST). All treatments were able to decrease the anxiety index assessed by the elevated plus maze (EPM) test. The activity, gene expression, and protein density of AChE were increased in the CRS model compared to control males. Overall, quercetin and TCP proved to reverse CRS-induced alterations in these parameters. Conclusions: Quercetin mitigated cognitive deficits, behavioral impairments, and neurochemical alterations induced by the CRS model, especially in association with TCP, supporting its potential as a promising therapeutic agent for depression.<\/jats:p>","DOI":"10.3390\/brainsci15070709","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T07:42:06Z","timestamp":1751355726000},"page":"709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quercetin and Tranylcypromine Improve Memory, Behavioral Performance, and Cholinergic Function in Male Rats Subjected to Chronic Restraint Stress"],"prefix":"10.3390","volume":"15","author":[{"given":"Vitor Bastianello","family":"Mostardeiro","sequence":"first","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3524-3446","authenticated-orcid":false,"given":"Charles Elias","family":"Assmann","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8940-9565","authenticated-orcid":false,"given":"Adriel Antonio","family":"Schirmann","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcylene Vieira","family":"da Silveira","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9770-3021","authenticated-orcid":false,"given":"Bianca Vedoin Cop\u00eas","family":"Rambo","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mairin","family":"Schott","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline da Silva","family":"Pereira","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5266-7534","authenticated-orcid":false,"given":"Vanessa Val\u00e9ria","family":"Miron","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heloiza Winck","family":"Soares","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa Varotto","family":"Dambr\u00f3s","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina Fontana","family":"Belinazo","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamires Gelatti","family":"Vidal","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarete Dulce","family":"Bagatini","sequence":"additional","affiliation":[{"name":"Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul (UFFS), Chapec\u00f3 89815-899, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5240-8935","authenticated-orcid":false,"given":"Maria Rosa Chitolina","family":"Schetinger","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera Maria Melchiors","family":"Morsch","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2025, March 07). 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