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Are NMDA Antagonists or Venlafaxine More Effective in the Forced Swimming Test?

Year 2025, Volume: 22 Issue: 2, 233 - 238

Ahmet İnal , Aydın Erenmemişoğlu

https://doi.org/10.35440/hutfd.1617126

Abstract

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.

Keywords

Amantadine Folic acid Depression NMDA Zinc venlafaxine

Ethical Statement

This study was conducted with the required authorization and consent from the Erciyes University Faculty of Medicine Ethics Committee(No: 01/175, dated 02.05.2006).

Supporting Institution

The Scientific Research Projects Unit of Erciyes University

Project Number

TT-06-35

Thanks

We would like to thank the Erciyes University Faculty of Medicine Department of Medical Pharmacology staff (Dr. Zafer Sezer and Dr. Nuran Küçük) for their support in this study. We would like to thank Ahmet Öztürk for the statistical analysis.

References

  • 1. Bender A, Hagan KE, Kingston N. The association of folic acid and depression: A meta-analysis. J Psychiatr Res. 2017; 95: 9-18.
  • 2. Zhang Y, Chen Y, Ma L. Depression and cardiovascular disease in elderly: Current understanding. J Clin Neurosci. 2018;47:1-5.
  • 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.
  • 4. Howard p, Twycross R, Shuster J, Mihalyo M, Wilcock A. Antidepressant drugs. J Pain Symptom Manage. 2012 Nov;44(5):763-83.
  • 5. McIntyre RS, Jain R. Glutamatergic Modulators for Major Depression from Theory to Clinical Use. CNS Drugs. 2024;38(11):869-890.
  • 6. Williams NR, Schatzberg AF. NMDA antagonist treatment of depression. Curr Opin Neurobiol. 2016; 36:112-117.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 19. Kovich H, Kim W, Quaste AM. Pharmacologic Treatment of Depression . Am Fam Physician. 2023; 107(2): 173-181.
  • 20. Pochwat B, Nowak G, Szewczyk B. An update on NMDA anta-gonists in depression. Expert Rev Neurother. 2019 Nov;19(11):1055-1067.
  • 21. Moryl E, Danysz W, Quack G. Potential antidepressive pro-perties of amantadine, memantine and bifemelane. Pharma-col. Toxicol. 1993; 72: 394-397.
  • 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.
  • 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.
  • 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.
  • 25. Williams NR, Schatzberg AF. NMDA antagonist treatment of depression. Current Opinion in Neurobiology. 2016; 36: 112-117.
  • 26. Mlyniec K. Zinc sulfate in the Glutamatergic Theory of Dep-ression. Curr Neuropharmacol. 2015;13(4):505-13.
  • 27. Bobula B, Hess G. Antidepressant treatments-induced modi-fications of glutamatergic transmission in rat frontal cortex. Pharmacol Rep. 2008;60(6):865-71.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.

NMDA Antagonistleri mi Venlafaksin mi Zorlu Yüzme Testinde Daha Etkili?

Year 2025, Volume: 22 Issue: 2, 233 - 238

Ahmet İnal , Aydın Erenmemişoğlu

https://doi.org/10.35440/hutfd.1617126

Abstract

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.

Keywords

Amantadin Folik asit Depresyon NMDA Çinko venlafaksin

Project Number

TT-06-35

References

  • 1. Bender A, Hagan KE, Kingston N. The association of folic acid and depression: A meta-analysis. J Psychiatr Res. 2017; 95: 9-18.
  • 2. Zhang Y, Chen Y, Ma L. Depression and cardiovascular disease in elderly: Current understanding. J Clin Neurosci. 2018;47:1-5.
  • 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.
  • 4. Howard p, Twycross R, Shuster J, Mihalyo M, Wilcock A. Antidepressant drugs. J Pain Symptom Manage. 2012 Nov;44(5):763-83.
  • 5. McIntyre RS, Jain R. Glutamatergic Modulators for Major Depression from Theory to Clinical Use. CNS Drugs. 2024;38(11):869-890.
  • 6. Williams NR, Schatzberg AF. NMDA antagonist treatment of depression. Curr Opin Neurobiol. 2016; 36:112-117.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 19. Kovich H, Kim W, Quaste AM. Pharmacologic Treatment of Depression . Am Fam Physician. 2023; 107(2): 173-181.
  • 20. Pochwat B, Nowak G, Szewczyk B. An update on NMDA anta-gonists in depression. Expert Rev Neurother. 2019 Nov;19(11):1055-1067.
  • 21. Moryl E, Danysz W, Quack G. Potential antidepressive pro-perties of amantadine, memantine and bifemelane. Pharma-col. Toxicol. 1993; 72: 394-397.
  • 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.
  • 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.
  • 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.
  • 25. Williams NR, Schatzberg AF. NMDA antagonist treatment of depression. Current Opinion in Neurobiology. 2016; 36: 112-117.
  • 26. Mlyniec K. Zinc sulfate in the Glutamatergic Theory of Dep-ression. Curr Neuropharmacol. 2015;13(4):505-13.
  • 27. Bobula B, Hess G. Antidepressant treatments-induced modi-fications of glutamatergic transmission in rat frontal cortex. Pharmacol Rep. 2008;60(6):865-71.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
There are 33 citations in total.

Details

Primary Language English
Subjects Medical Pharmacology
Journal Section Research Article
Authors

Ahmet İnal 0000-0002-5917-3729

Aydın Erenmemişoğlu 0000-0002-9277-1333

Project Number TT-06-35
Early Pub Date May 27, 2025
Publication Date
Submission Date January 13, 2025
Acceptance Date April 29, 2025
Published in Issue Year 2025 Volume: 22 Issue: 2

Cite

Vancouver İnal A, Erenmemişoğlu A. Are NMDA Antagonists or Venlafaxine More Effective in the Forced Swimming Test?. Harran Üniversitesi Tıp Fakültesi Dergisi. 2025;22(2):233-8.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty