Research Article
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Investigation of The Learning and Memory Enhancing Effects of 0.25 mA and 0.5 mA Anodal and Cathodal Transcranial Direct Current Stimulations in Healthy Rats

Year 2023, , 98 - 110, 28.02.2023
https://doi.org/10.19127/mbsjohs.1207315

Abstract

Objective: Our aim in this study was to investigate the effects of tDCS, which is known to be effective on AM-PA and NMDA, with different anodal and cathodal stimulation types and 0.25 mA and 0.5 mA current intensi-ties on learning and memory by behavioral and molecular mechanisms.

Methods: 50 male Wistar rats weighing 290-310 g were divided into 5 groups as control, C1-tDCS, C2-tDCS, A1-tDCS and A2-tDCS. In the C1-tDCS group, 0.25 mA cathodal tDCS stimulation for 30 min per day for 5 days, in the C2-tDCS group for 30 min per day for 0.5 mA cathodal tDCS stimulation for 5 days, in the A1-tDCS group for 5 days with 0.25 mA anodal tDCS stimulation for 30 min per day and A2-tDCS group The tDCS group received 0.5 mA anodal tDCS stimulation for 30 minutes per day for 5 days. On the 6th and 7th days of the experiment, the locomotor activity, learning and memory behaviors of the rats were evaluated by open field test, y maze test and object localization test. In addition, glutamate levels were measured in hippocampus tis-sues by ELISA method.

Results: It was observed that there were non-significant decreases in the results of the C1-tDCS and C2-tDCS groups in which cathodal stimulation was applied compared to the control group in locomotor activity, learning and memory data. On the other hand, an increase was observed in the data of the A1-tDCS and A2-tDCS groups in which anodal stimulation was applied, and the increase in the data of the A2-tDCS group from these groups was found to be statistically significant compared to the control (p<0.05). Similar results were also seen in glu-tamate levels. A non-significant decrease in glutamate levels was observed in the C1-tDCS and C2-tDCS groups compared to the control, while an insignificant increase in glutamate levels in the A1-tDCS group was observed. On the other hand, there was a significant increase in glutamate level in the A1-tDCS group compared to the control group (p<0.05).

Conclusion: In conclusion, our data showed that 0.5 mA anodal tDCS stimulation for 30 min for 5 days can enhance learning and memory on the glutamatergic pathway.

Thanks

Thanks to Prof. Dr. N. Derin for their support.

References

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  • 2. Nitsche MA, Paulus W. Excitability chan-ges induced in the human motor cortex by weak transcranial direct current stimula-tion. J Physiol. 2000;527 Pt 3:633-9.
  • 3. Purpura DP, McMurtry JG. Intracellular Activities and Evoked Potential Changes during Polarization of Motor Cortex. J Ne-urophysiol. 1965;28:166-85.
  • 4. Arul-Anandam AP, Loo C, Sachdev P. Transcranial direct current stimulation - what is the evidence for its efficacy and sa-fety? F1000 Med Rep. 2009;1.
  • 5. Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, et al. Transc-ranial direct current stimulation: State of the art 2008. Brain Stimul. 2008;1(3):206-23.
  • 6. Tarlaci S, Turman B. Use of Non-Invasive Brain Stimulation in Stroke. In: Carrillo-Ruiz JD, editor. Topics in Neuromodula-tion Treatment. First Edt ed. Janeza Trdine 9, 51000 Rijeka, Croatia2012.
  • 7. Fregni F, Thome-Souza S, Nitsche MA, Freedman SD, Valente KD, Pascual-Leone A. A controlled clinical trial of cathodal DC polarization in patients with refractory epilepsy. Epilepsia. 2006;47(2):335-42.
  • 8. Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJ, Lima MC, et al. Transc-ranial direct current stimulation of the unaffected hemisphere in stroke patients. Neuroreport. 2005;16(14):1551-5.
  • 9. Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, et al. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain. 2005;128(Pt 3):490-9.
  • 10. Akcay G, Derin N. The Effects of tDCS on Depression and Anxiety Disorders Induced by Sub-Chronic Stress. Turk Hij Den Biyol Derg. 2022;79(2):267-78.
  • 11. Miranda PC, Lomarev M, Hallett M. Modeling the current distribution during transcranial direct current stimulation. Clin Neurophysiol. 2006;117(7):1623-9.
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  • 13. Marquez-Ruiz J, Leal-Campanario R, Sanchez-Campusano R, Molaee-Ardekani B, Wendling F, Miranda PC, et al. Transc-ranial direct-current stimulation modulates synaptic mechanisms involved in associa-tive learning in behaving rabbits. Proc Natl Acad Sci U S A. 2012;109(17):6710-5.
  • 14. Floel A, Suttorp W, Kohl O, Kurten J, Lohmann H, Breitenstein C, et al. Non-invasive brain stimulation improves ob-ject-location learning in the elderly. Neu-robiol Aging. 2012;33(8):1682-9.
  • 15. Stagg CJ, Antal A, Nitsche MA. Phy-siology of Transcranial Direct Current Stimulation. J ECT. 2018;34(3):144-52.
  • 16. Medeiros LF, de Souza IC, Vidor LP, de Souza A, Deitos A, Volz MS, et al. Neu-robiological effects of transcranial direct current stimulation: a review. Front Psyc-hiatry. 2012;3:110.
  • 17. Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimula-tion. Neuroscientist. 2011;17(1):37-53.
  • 18. Alonzo A, Brassil J, Taylor JL, Martin D, Loo CK. Daily transcranial direct cur-rent stimulation (tDCS) leads to greater increases in cortical excitability than se-cond daily transcranial direct current sti-mulation. Brain Stimulation. 2012;5(3):208-13.
  • 19. Galvez V, Alonzo A, Martin D, Loo CK. Transcranial direct current stimulation treatment protocols: should stimulus inten-sity be constant or incremental over mul-tiple sessions? Int J Neuropsychopharma-col. 2013;16(1):13-21.
  • 20. Valle A, Roizenblatt S, Botte S, Zaghi S, Riberto M, Tufik S, et al. Efficacy of anodal transcranial direct current stimula-tion (tDCS) for the treatment of fibrom-yalgia: results of a randomized, sham-controlled longitudinal clinical trial. J Pain Manag. 2009;2(3):353-61.
  • 21. Roizenblatt S, Fregni F, Gimenez R, Wetzel T, Rigonatti SP, Tufik S, et al. Site-specific effects of transcranial direct cur-rent stimulation on sleep and pain in fib-romyalgia: a randomized, sham-controlled study. Pain Pract. 2007;7(4):297-306.
  • 22. Nitsche MA, Paulus W. Sustained excitability elevations induced by transc-ranial DC motor cortex stimulation in hu-mans. Neurology. 2001;57(10):1899-901.
  • 23. Webster JP, Lamberton PH, Donnelly CA, Torrey EF. Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on Toxoplas-ma gondii's ability to alter host behaviour. Proc Biol Sci. 2006;273(1589):1023-30.
  • 24. Akçay G, Derin N. The Effects of tDCS on Depression and Anxiety Disorders Induced by Sub-Chronic Stress. Turk Hij Den Biyol Derg. 2022;79(2):267-278
  • 25. Ogut E, Akcay G, Yildirim FB, Derin N, Aslan M. The influence of syringic acid treatment on total dopamine levels of the hippocampus and on cognitive behavioral skills. Int J Neurosci. 2020:1-9.
  • 26. Bindman LJ, Lippold OC, Redfearn JW. Long-lasting changes in the level of the electrical activity of the cerebral cortex produced bypolarizing currents. Nature. 1962;196:584-5.
  • 27. Habich A, Slotboom J, Peter J, Wiest R, Klöppel S. No Effect of Anodal tDCS on Verbal Episodic Memory Performance and Neurotransmitter Levels in Young and El-derly Participants. Neural plasticity. 2020;2020:8896791.
  • 28. Luo Y, Yang W, Li N, Yang X, Zhu B, Wang C, et al. Anodal Transcranial Direct Current Stimulation Can Improve Spatial Learning and Memory and Attenuate Aβ(42) Burden at the Early Stage of Alzhe-imer's Disease in APP/PS1 Transgenic Mi-ce. Frontiers in aging neuroscience. 2020;12:134.
  • 29. Au J, Smith-Peirce RN, Carbone E, Moon A, Evans M, Jonides J, et al. Effects of Multisession Prefrontal Transcranial Di-rect Current Stimulation on Long-term Memory and Working Memory in Older Adults. Journal of cognitive neuroscience. 2022;34(6):1015-37.
  • 30. Roostaei A, Vaezi G, Nasehi M, Haeri-Rohani A, Zarrindast MR. The Involve-ment of D1 and D2 Dopamine Receptors in the Restoration Effect of Left Frontal Ano-dal, but not Cathodal, tDCS on Streptozo-cin-Induced Amnesia. Archives of Iranian medicine. 2019;22(3):144-54.
  • 31. Yu X, Li Y, Wen H, Zhang Y, Tian X. Intensity-dependent effects of repetitive anodal transcranial direct current stimula-tion on learning and memory in a rat model of Alzheimer's disease. Neurobiol Learn Mem. 2015;123:168-78.
  • 32. Zhang K, Guo L, Zhang J, An G, Zhou Y, Lin J, et al. A safety study of 500 μA cathodal transcranial direct current stimu-lation in rat. BMC Neurosci. 2019;20(1):40.
  • 33. Mehrsafar AH, Rosa MAS, Zadeh AM, Gazerani P. A feasibility study of applica-tion and potential effects of a single ses-sion transcranial direct current stimulation (tDCS) on competitive anxiety, mood state, salivary levels of cortisol and alpha amyla-se in elite athletes under a real-world com-petition. Physiol Behav. 2020;227:113173.
  • 34. Bogdanov M, Schwabe L. Transcranial Stimulation of the Dorsolateral Prefrontal Cortex Prevents Stress-Induced Working Memory Deficits. J Neurosci. 2016;36(4):1429-37.
Year 2023, , 98 - 110, 28.02.2023
https://doi.org/10.19127/mbsjohs.1207315

Abstract

References

  • 1. Danbolt NC. Glutamate uptake. Prog Neu-robiol. 2001;65(1):1-105.
  • 2. Nitsche MA, Paulus W. Excitability chan-ges induced in the human motor cortex by weak transcranial direct current stimula-tion. J Physiol. 2000;527 Pt 3:633-9.
  • 3. Purpura DP, McMurtry JG. Intracellular Activities and Evoked Potential Changes during Polarization of Motor Cortex. J Ne-urophysiol. 1965;28:166-85.
  • 4. Arul-Anandam AP, Loo C, Sachdev P. Transcranial direct current stimulation - what is the evidence for its efficacy and sa-fety? F1000 Med Rep. 2009;1.
  • 5. Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, et al. Transc-ranial direct current stimulation: State of the art 2008. Brain Stimul. 2008;1(3):206-23.
  • 6. Tarlaci S, Turman B. Use of Non-Invasive Brain Stimulation in Stroke. In: Carrillo-Ruiz JD, editor. Topics in Neuromodula-tion Treatment. First Edt ed. Janeza Trdine 9, 51000 Rijeka, Croatia2012.
  • 7. Fregni F, Thome-Souza S, Nitsche MA, Freedman SD, Valente KD, Pascual-Leone A. A controlled clinical trial of cathodal DC polarization in patients with refractory epilepsy. Epilepsia. 2006;47(2):335-42.
  • 8. Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJ, Lima MC, et al. Transc-ranial direct current stimulation of the unaffected hemisphere in stroke patients. Neuroreport. 2005;16(14):1551-5.
  • 9. Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, et al. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain. 2005;128(Pt 3):490-9.
  • 10. Akcay G, Derin N. The Effects of tDCS on Depression and Anxiety Disorders Induced by Sub-Chronic Stress. Turk Hij Den Biyol Derg. 2022;79(2):267-78.
  • 11. Miranda PC, Lomarev M, Hallett M. Modeling the current distribution during transcranial direct current stimulation. Clin Neurophysiol. 2006;117(7):1623-9.
  • 12. Wagner T, Fregni F, Fecteau S, Grod-zinsky A, Zahn M, Pascual-Leone A. Transcranial direct current stimulation: a computer-based human model study. Neu-roimage. 2007;35(3):1113-24.
  • 13. Marquez-Ruiz J, Leal-Campanario R, Sanchez-Campusano R, Molaee-Ardekani B, Wendling F, Miranda PC, et al. Transc-ranial direct-current stimulation modulates synaptic mechanisms involved in associa-tive learning in behaving rabbits. Proc Natl Acad Sci U S A. 2012;109(17):6710-5.
  • 14. Floel A, Suttorp W, Kohl O, Kurten J, Lohmann H, Breitenstein C, et al. Non-invasive brain stimulation improves ob-ject-location learning in the elderly. Neu-robiol Aging. 2012;33(8):1682-9.
  • 15. Stagg CJ, Antal A, Nitsche MA. Phy-siology of Transcranial Direct Current Stimulation. J ECT. 2018;34(3):144-52.
  • 16. Medeiros LF, de Souza IC, Vidor LP, de Souza A, Deitos A, Volz MS, et al. Neu-robiological effects of transcranial direct current stimulation: a review. Front Psyc-hiatry. 2012;3:110.
  • 17. Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimula-tion. Neuroscientist. 2011;17(1):37-53.
  • 18. Alonzo A, Brassil J, Taylor JL, Martin D, Loo CK. Daily transcranial direct cur-rent stimulation (tDCS) leads to greater increases in cortical excitability than se-cond daily transcranial direct current sti-mulation. Brain Stimulation. 2012;5(3):208-13.
  • 19. Galvez V, Alonzo A, Martin D, Loo CK. Transcranial direct current stimulation treatment protocols: should stimulus inten-sity be constant or incremental over mul-tiple sessions? Int J Neuropsychopharma-col. 2013;16(1):13-21.
  • 20. Valle A, Roizenblatt S, Botte S, Zaghi S, Riberto M, Tufik S, et al. Efficacy of anodal transcranial direct current stimula-tion (tDCS) for the treatment of fibrom-yalgia: results of a randomized, sham-controlled longitudinal clinical trial. J Pain Manag. 2009;2(3):353-61.
  • 21. Roizenblatt S, Fregni F, Gimenez R, Wetzel T, Rigonatti SP, Tufik S, et al. Site-specific effects of transcranial direct cur-rent stimulation on sleep and pain in fib-romyalgia: a randomized, sham-controlled study. Pain Pract. 2007;7(4):297-306.
  • 22. Nitsche MA, Paulus W. Sustained excitability elevations induced by transc-ranial DC motor cortex stimulation in hu-mans. Neurology. 2001;57(10):1899-901.
  • 23. Webster JP, Lamberton PH, Donnelly CA, Torrey EF. Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on Toxoplas-ma gondii's ability to alter host behaviour. Proc Biol Sci. 2006;273(1589):1023-30.
  • 24. Akçay G, Derin N. The Effects of tDCS on Depression and Anxiety Disorders Induced by Sub-Chronic Stress. Turk Hij Den Biyol Derg. 2022;79(2):267-278
  • 25. Ogut E, Akcay G, Yildirim FB, Derin N, Aslan M. The influence of syringic acid treatment on total dopamine levels of the hippocampus and on cognitive behavioral skills. Int J Neurosci. 2020:1-9.
  • 26. Bindman LJ, Lippold OC, Redfearn JW. Long-lasting changes in the level of the electrical activity of the cerebral cortex produced bypolarizing currents. Nature. 1962;196:584-5.
  • 27. Habich A, Slotboom J, Peter J, Wiest R, Klöppel S. No Effect of Anodal tDCS on Verbal Episodic Memory Performance and Neurotransmitter Levels in Young and El-derly Participants. Neural plasticity. 2020;2020:8896791.
  • 28. Luo Y, Yang W, Li N, Yang X, Zhu B, Wang C, et al. Anodal Transcranial Direct Current Stimulation Can Improve Spatial Learning and Memory and Attenuate Aβ(42) Burden at the Early Stage of Alzhe-imer's Disease in APP/PS1 Transgenic Mi-ce. Frontiers in aging neuroscience. 2020;12:134.
  • 29. Au J, Smith-Peirce RN, Carbone E, Moon A, Evans M, Jonides J, et al. Effects of Multisession Prefrontal Transcranial Di-rect Current Stimulation on Long-term Memory and Working Memory in Older Adults. Journal of cognitive neuroscience. 2022;34(6):1015-37.
  • 30. Roostaei A, Vaezi G, Nasehi M, Haeri-Rohani A, Zarrindast MR. The Involve-ment of D1 and D2 Dopamine Receptors in the Restoration Effect of Left Frontal Ano-dal, but not Cathodal, tDCS on Streptozo-cin-Induced Amnesia. Archives of Iranian medicine. 2019;22(3):144-54.
  • 31. Yu X, Li Y, Wen H, Zhang Y, Tian X. Intensity-dependent effects of repetitive anodal transcranial direct current stimula-tion on learning and memory in a rat model of Alzheimer's disease. Neurobiol Learn Mem. 2015;123:168-78.
  • 32. Zhang K, Guo L, Zhang J, An G, Zhou Y, Lin J, et al. A safety study of 500 μA cathodal transcranial direct current stimu-lation in rat. BMC Neurosci. 2019;20(1):40.
  • 33. Mehrsafar AH, Rosa MAS, Zadeh AM, Gazerani P. A feasibility study of applica-tion and potential effects of a single ses-sion transcranial direct current stimulation (tDCS) on competitive anxiety, mood state, salivary levels of cortisol and alpha amyla-se in elite athletes under a real-world com-petition. Physiol Behav. 2020;227:113173.
  • 34. Bogdanov M, Schwabe L. Transcranial Stimulation of the Dorsolateral Prefrontal Cortex Prevents Stress-Induced Working Memory Deficits. J Neurosci. 2016;36(4):1429-37.
There are 34 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research articles
Authors

Güven Akçay 0000-0003-3418-8825

Publication Date February 28, 2023
Published in Issue Year 2023

Cite

Vancouver Akçay G. Investigation of The Learning and Memory Enhancing Effects of 0.25 mA and 0.5 mA Anodal and Cathodal Transcranial Direct Current Stimulations in Healthy Rats. Mid Blac Sea J Health Sci. 2023;9(1):98-110.

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