TY - JOUR T1 - Are NMDA Antagonists or Venlafaxine More Effective in the Forced Swimming Test? TT - NMDA Antagonistleri mi Venlafaksin mi Zorlu Yüzme Testinde Daha Etkili? AU - İnal, Ahmet AU - Erenmemişoğlu, Aydın PY - 2025 DA - June Y2 - 2025 DO - 10.35440/hutfd.1617126 JF - Harran Üniversitesi Tıp Fakültesi Dergisi PB - Harran Üniversitesi WT - DergiPark SN - 1304-9623 SP - 233 EP - 238 VL - 22 IS - 2 LA - en AB - Background: The aim of this study is to compare the antidepressant-like effects of NMDA anta-gonists (zinc sulfate, amantadine, and folic acid) with venlafaxine.Materials and Methods: Ninety-six male Swiss Albino mice were used in the experiments and divided into experimental groups. To assess depression-like behaviors in the animals, the forced swim test was performed. The effects of the drugs on locomotor activity were measured using the open field test.Results: No differences were found between venlafaxine, folic acid, or zinc sulfate when admi-nistered alone in the experimental depression model. When administered in combination, the highest antidepressant-like effect was observed in the zinc-amantadine combination and the zinc sulfate-amantadine-folic acid combination. When venlafaxine and folic acid were adminis-tered together, the antidepressant-like effect was greater compared to other venlafaxine com-binations.Conclusions: The use of these combinations in the treatment of depression is important for the enhancement of antidepressant efficacy. KW - Amantadine KW - Folic acid KW - Depression KW - NMDA KW - Zinc KW - venlafaxine N2 - Amaç: Bu çalışmada NMDA antagonistlerinin (çinko sülfat, amantadin ve folik asit) antidepresan benzeri etkilerinin venlafaksin ile karşılaştırılması amaçlanmıştır.Materyal ve Metod: Deneylerde doksan altı Swiss Albino erkek fare kullanıldı ve deney grupları-na ayrıldı. Hayvanların depresyon benzeri davranışlarını test etmek amacıyla zorlu yüzme testi yapıldı. İlaçların lokomotor aktivite üzerindeki etkileri açık alan testi kullanılarak ölçüldü.Bulgular: Venlafaksin, folik asit veya çinko sülfat tek başına uygulandığında aralarında deneysel depresyon modelinde fark bulunmadı. Kombinasyon halinde uygulandığında en yüksek antidep-resan benzeri etki çinko sülfat-amantadin kombinasyonunda ve çinko sülfat-amantadin-folik asit kombinasyonunda gözlendi. Venlafaksin ve folik asit birlikte uygulandığında antidepresan benze-ri etki diğer venlafaksin kombinasyonlarına göre daha fazlaydı.Sonuç: Bu kombinasyonların depresyon tedavisinde kullanılması antidepresan etkinliğin artışı açısından önemlidir. CR - 1. Bender A, Hagan KE, Kingston N. The association of folic acid and depression: A meta-analysis. J Psychiatr Res. 2017; 95: 9-18. CR - 2. Zhang Y, Chen Y, Ma L. Depression and cardiovascular disease in elderly: Current understanding. J Clin Neurosci. 2018;47:1-5. CR - 3. Rotenstein LS, Ramos MA, Torre M, Segal JB, Peluso MJ, Guille C et al. Prevalence of Depression, Depressive Symp-toms, and Suicidal Ideation Among Medical Students: A Sys-tematic Review and Meta-Analysis. JAMA. 2016;316(21):2214-2236. CR - 4. Howard p, Twycross R, Shuster J, Mihalyo M, Wilcock A. Antidepressant drugs. J Pain Symptom Manage. 2012 Nov;44(5):763-83. CR - 5. McIntyre RS, Jain R. Glutamatergic Modulators for Major Depression from Theory to Clinical Use. CNS Drugs. 2024;38(11):869-890. CR - 6. Williams NR, Schatzberg AF. NMDA antagonist treatment of depression. Curr Opin Neurobiol. 2016; 36:112-117. CR - 7. Refaey HE, Al Amri HS, Ashour AE, Ahmed AF. Administration of Zinc sulfate with Paroxetine Improved the Forced Swim Test Behavioral Pattern of Treated Mice in Acute and Sub-Acute Study. Journal of Behavioral and Brain Science. 2015; 5: 213-220. CR - 8. Maj J, Rogoz Z, Skuza G, Sowinska H. The effects of CGP 37849 and CGP 39551, competitive NMDA antagonists, in the forced swimming test. Pol. J. Pharmacol. Pharm. 1992; 44:337-346. CR - 9. 9.Wang J, Um P, Dickerman BA, Liu J. Zinc sulfate, Magne-sium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications. Nutrients. 2018;10(5),584:1-19. CR - 10. Maes M, Vandoolaeghe E, Neels H, Demedts P, Wauters A, Meltzer HY, et al. Lower serum zinc sulfate in major depres-sion is a sensitive marker of treatment resistance and of the immune-inflammatory response in that illness. Biol. Psychi-atry.1997; 42:349-358. CR - 11. Yosaee S, Clark CCT, Keshtkaran Z, Ashourpour LM, Keshani P, SoltaniS. Zinc sulfate in depression: From development to treatment. A comparative/ dose response meta-analysis of observational studies and randomized controlled trials. Gen Hosp Psychiatry. 2022; 74: 110-117. CR - 12. Petrilli MA, Kranz TM, Kleinhaus K, Joe P, Getz M, Johnson P, et al. The Emerging Role for Zinc sulfate in Depression and Psychosis . Front Pharmacol. 2017; 30(8):414. CR - 13. Jamerson BD, Payne RD, Garrett ME, Ashley-Koch AE, Speer MC, Steffens DC. Folic acid Metabolism Genes, Dietary Folic acid and Response to Antidepressant Medications in Late-Life Depression. Int J Geriatr Psychiatry. 2013; 28: 925-932. CR - 14. Liwinski T, Lang UE. Folic acid and Its Significance in Depres-sive Disorders and Suicidality: A Comprehensive Narrative Review. Nutrients. 2023;15(17):3859. CR - 15. Inara FRB, Vital MA, Galduróz JC, Andreatini R. Potential antidepressant effect of amantadine: a review of preclinical studies and clinical trials. Braz J Psychiatry. 2018;40(4):449-458. CR - 16. Furukawa TA, Cipriani A, Cowen PJ, Leucht S, Egger M, Salanti G. Optimal dose of selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine in major depression: a systema-tic review and dose-response meta-analysis Lancet Psychiatry . 2019;6(7):601-609. CR - 17. Porsolt RD, Bertin A, Jalfre M. Behavioural despair in rats and mice: Strain differences and the effects of imipramine. Eur J Pharmacol. 1978; 51:291-4. CR - 18. Mogilnicka E, Czyrak A, Maj J. Dihydropyridine calcium chan-nel antagonists reduce immobility in the mouse behavioral despair test; antidepressants facilitate nifedipine action. Eur J Pharmacol. 1987; 138: 413- 416. CR - 19. Kovich H, Kim W, Quaste AM. Pharmacologic Treatment of Depression . Am Fam Physician. 2023; 107(2): 173-181. CR - 20. Pochwat B, Nowak G, Szewczyk B. An update on NMDA anta-gonists in depression. Expert Rev Neurother. 2019 Nov;19(11):1055-1067. CR - 21. Moryl E, Danysz W, Quack G. Potential antidepressive pro-perties of amantadine, memantine and bifemelane. Pharma-col. Toxicol. 1993; 72: 394-397. CR - 22. Zanos P, Brown KA, Georgiou P, Yuan P, Zarate CA, Thompson SM, et al. NMDA Receptor Activation-Dependent Antidepres-sant-Relevant Behavioral and Synaptic Actions of Ketamine. J Neurosci. 2023;43(6):1038-1050. CR - 23. Szewczyk B, Branski P, Wieronska JM, Pałucha A, Pilc A, Nowak G. İnteraction of zinc sulfate with antidepressants in the forced swimming test in mice. Pol J Pharmacol. 2002; 54: 681-685. CR - 24. Berman RM, Capiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in dep-ressed patients . Biol. Psychiatry. 2000; 47: 351-354. CR - 25. Williams NR, Schatzberg AF. NMDA antagonist treatment of depression. Current Opinion in Neurobiology. 2016; 36: 112-117. CR - 26. Mlyniec K. Zinc sulfate in the Glutamatergic Theory of Dep-ression. Curr Neuropharmacol. 2015;13(4):505-13. CR - 27. Bobula B, Hess G. Antidepressant treatments-induced modi-fications of glutamatergic transmission in rat frontal cortex. Pharmacol Rep. 2008;60(6):865-71. CR - 28. Papakostas GI, Petersen T, Lebowitz BD, Mischoulon D, Ryan JL, Nierenberg AA, et al. The relationship between serum fo-lic acid, vitamin B12, and homocysteine levels in major dep-ressive disorder and the timing of improvement with flu-oxetine. Int J Neuropsychopharmacol. 2005; 8: 523-528. CR - 29. Lazarou C, Kapsou M. The role of folic acid in prevention and treatment of depression: an overview of existing evidence and implications for practice. Complement Ther Clin Pract. 2010;16(3):161-166 CR - 30. Fava M, Borus JS, Alpert JE, Nierenberg AA, Rosenbaum JF, Bottiglieri T. Folic acid, vitamin B12, and homocysteine in major depressive disorder . Am J Psychiatry. 1997; 154: 426-428. CR - 31. Thomas J, Khanam R, Vohora D. Augmentation of effect of venlafaxine by folic acid in behavioral paradigms of depres-sion in mice: Evidence of serotonergic and pro-inflammatory cytokine pathways. Pharmacol Rep. 2016 Apr;68(2):396-403. CR - 32. Rogoz Z, Skuza G, Maj J. Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats. Neuropharmacology. 2002; 42: 1024-1030. CR - 33. Mrozek W, Socha J, Sidorowicz K, Skrok A, Syrytczyk A, Piat-kowska-Chmiel I, et al. Pathogenesis and treatment of dep-ression: Role of diet in prevention and therapy. Nutrition. 2023 Nov;115:112143. UR - https://doi.org/10.35440/hutfd.1617126 L1 - https://dergipark.org.tr/tr/download/article-file/4509107 ER -