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Antidepressant-Like Effects of Ceftriaxone in Chronic Unpredictable Mild Stress Model in Rats: The Importance of Reuptake Time of Glutamate

Year 2019, Volume: 9 Issue: 4, 294 - 299, 31.12.2019
https://doi.org/10.33808/clinexphealthsci.613963

Abstract

Objective:
We aimed to indicate the relationship between depression and glutamate, and to
reveal the effect of escitalopram, an antidepressant, which is widely used in depression
treatment and reuptake parameters of glutamate, and to treat depression with
ceftriaxone, one of the beta lactam antibiotics which increased the number and
activity of glutamate transporters.



Methods: In CUMS, rats subjected to series
of different mild stressors in an unpredictable manner for
40 days. On the day 20 rats were
divided in to groups such as CUMS,
CUMS+Escitalopram and CUMS+Ceftriaxone. 4 weeks. Treatments were started at 2nd week of CUMS and continued
for 21 days. Anhedonia and antidepressant effect were assessed by sucrose
preference (SP), locomotor activity (LA), elevated plus maze (EPM) and forced
swim test (FST) at the end of the experiment respectively.
At the end of the experiment,
behavioral tests were made, and glutamate reuptake time in CA3 (cornuammonis 3)
brain region which are related with depression were measured by means of in
vivo voltammetry technique.



Results: Ceftriaxone
treatment had an antidepressant-like effect.
Escitalopram and ceftriaxone increased SP and locomotor
activity, reduced immobility FST, forced swim and time spent in closed arms in
EPM compared to CUMS group.
In this in-vivo voltametric study, it was also observed that there was a
significant decrease in glutamate reuptake time in depression.



Conclusion: Escitalopram
and ceftriaxone demonstrated
antidepressant-like effects by reversing behavioral changes in CUMS model. Escitalopram
treatment in CA3 region corrected the decrease in glutamate reuptake time which
is consistent with
the hypothesis that enhanced uptake of glutamate might have antidepressant-like
effects.

Supporting Institution

TUBITAK

Project Number

113S083

Thanks

This study was supported by TUBITAK with project number 113S083. We would like to thank TUBITAK for their support in carrying out the study. A part of this study was presented at international congress by 27nd Europan Collage of Neuropsychopharmacology (ECNP) Berlin, Germany, 2014.

References

  • 1. Skolnick P, Legutko B, Li X, Bymaster FP. Current perspectives on the development of non-biogenic amine-based antidepressants. Pharmacol Res 2001; 43(5): 411-23.
  • 2. Kulkarni SK and Dhir A. Current investigational drugs for major depression, Expert Opin Investig Drugs 2009; 18(6): 767-88.
  • 3. Lee TS, Quek SY and Krishnan KR. Molecular Imaging for Depressive Disorders, AJNR Am J Neuroradiol 2014; 35(6): 44-54.
  • 4. Arciniegas DB, Anderson CA, Topkoff J, McAllister TW. Mild traumatic brain injury: a neuropsychiatric approach to diagnosis, evaluation, and treatment, Neuropsychiatr Dis Treat 2005; 1(4): 311–327.
  • 5. Duman RS. Pathophysiology of depression and innovative treatments: remodelling glutamatergic synaptic connections, Dialogues in Clinical neuroscience 2014; 16: 11-27.
  • 6. Zhu X, Ye G, Wang Z , Luo J, Hao X. Sub-anesthetic doses of ketamine exert antidepressant-like effects and upregulate the expression of glutamate transporters in the hippocampus of rats, Neuroscience Letters 2017; 639(3): 132–137.
  • 7. Czéh B, Fuchs E, Wiborg O, Simong M. Animal models of major depression and their clinical implications, Progress in Neuro-Psychopharmacology and Biological Psychiatry 2016; 64: 293-310.
  • 8. Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation, Psychopharmacology 1997; 134(4): 319–329.
  • 9. Willner P. Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS, Neuropsychobiology 2005; 52: 90–110.
  • 10. Willner et al., Chronic mild stress-induced anhedonia: A realistic animal model of depression, Neuroscience & Biobehavioral Reviews 1992; 16 (4): 525-534.
  • 11. Helena M. Abelaira HM, Reus GZ, Quevedo J. Animal models as tools to study the pathophysiology of depression, Rev Bras Psiquiatr 2013; 35(2): 112-120.
  • 12. Deussing JM. Animal models of depression, Drug Discovery Today: Disease Models 2006; 3(4): 375-383.
  • 13. Wiborg O. Chronic mild stress for modeling anhedonia, Cell and Tissue Research 2013; 354(1): 155–169.
  • 14. Haapakoski R, Ebmeier KP, Aleniusc H,Kivimäki M. Innate and adaptive immunity in the development of depression: An update on current knowledge and technological advances, Progress in Neuro-Psychopharmacology and Biological Psychiatry 2016; 66: 63-72.
  • 15. Kaufmann FN, Costa AP, Ghisleni G, Diaz AP, Rodrigues ALS, Peluffo H, Kaster MP. NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings, Brain Behav Immun. 2017; 64: 367-383.
  • 16. Valtcheva S and Venance L. Astrocytes gate Hebbian synaptic plasticity in the striatum, Nat Commun 2016; 20(7): 1-17.
  • 17. Willner P, Towell A, Sampson D, Sophokleous S, Muscat R. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant, Psychopharmacology 1987; 93(3): 358-364.
  • 18. Yazir Y, Utkan T, and Aricioglu F. Inhibition of neuronal nitric oxide synthase and soluble guanylate cyclase prevents depression-like behaviour in rats exposed to chronic unpredictable mild stres, Basic Clin Pharmacol Toxicol 2012; 111(3): 154-60.
  • 19. Jiang P, Zhang WY, Li HD, Cai HL, Liu YP, Chen LY. Stress and vitamin D: altered vitamin D metabolism in both the hippocampus and myocardium of chronic unpredictable mild stress exposed rats, Psychoneuroendocrinology 2013; 38(10): 2091-2098.
  • 20. Nollet M, Le Guisquet AM, Belzung C. Models of depression: unpredictable chronic mild stress in mice, Curr Protoc Pharmacol. 2013; 5: 5.
  • 21. Burmeister J, Kota C, Maughan RL, Spokas JJ, Coderre JA, Ma R, Wielopolski L. A conducting plastic simulating brain tissue, Med Phys 2000; 27(11): 2560-2564.
  • 22. Hacimuftuoglu A, Tatar A, Cetin D, Taspinar N, Saruhan F, Okkay U, Turkez H, Unal D, Stephens RL Jr, Suleyman H. Astrocyte/neuron ratio and its importance on glutamate toxicity: an in vitro voltammetric study, Cytotechnology 2016; 68(4): 1425-1433.
  • 23. Mitani H, Shirayama Y, Yamada T, Maeda K, Ashby CR, Kawahara R. Correlation between plasma levels of glutamate, alanine and serine with severity of depression, Progress in Neuro-Psychopharmacology & Biological Psychiatry 2006; 30: 1155-1158.
  • 24. Rothstein JD, Kammen VM, Levey AI, Martin LJ, Kuncl RW. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis, Annals of Neurology 1995; 38: 73-84.
  • 25. Stephens RL. Glutamate transporter activators as anti-nociceptive agents, The Eurasian Journal of Medicine 2011; 43: 182-185.
  • 26. Jaquins-Gerstl A and Michael AC. Comparison of the brain penetration injury associated with microdialysis and voltammetry, journal of neurosciences methods 2009; 183(2): 127-135.
  • 27. Medina A, Burke S, Thompson RC, Bunney W, Myers RM, Schatzberg A, Akil H, Watson SJ. Glutamate transporters: a key piece in the glutamate puzzle of major depressive disorder, Journal of Psychiatric Research 2013; 47: 1150-1156.
  • 28. Kim K, Seok-Guen L, Kegelman TP, Su ZZ, Das SK, Dash R, Dasgupta S, Barral PM, Hedvat M, PAUL Diaz P, Reed JC, Stebbins JL, Pellecchia M, Sarkar D, Fisher PB. Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics, J Cell Physiol 2011; 226(10): 2484-93.
  • 29. Tower DB and OM Young. The activities of butyrylcholinesterase and carbonic anhydrase, the rate of anaerobic glycolysis, and the question of a constant density of glial cells in cerebral cortices of various mammalian species from mouse to whale, J Neurochem 1973; 20(2): 269-78.
  • 30. Medina A, Burke S, Thompson RC, Bunney W, Myers RM, Schatzberg A, Akil H, Watson SJ. Glutamate transporters: a key piece in the glutamate puzzle of major depressive disorder. Journal of Psychiatric Researc 2013; 47: 1150-1156.
  • 31. Tordera RM, Garcia-Garcia AL, Elizalde N, Segura V, Aso E, Venzala E, Ramirez MJ, Del Rio J. Chronic stress and impaired glutamate function elicit a depressive-like phenotype and common changes in gene expression in the mouse frontal cortex. European Neuropsychopharmacology 2011; 21: 23-32.
  • 32. Yang H, Spence JS, Devous MD, Briggs RW, Goyal A, Xiao H, Yadav H, Adinoff B. Striatal-limbic activation is associated with intensity of anticipatory anxiety, Psychiatry Research 2012; 204: 123-131.
Year 2019, Volume: 9 Issue: 4, 294 - 299, 31.12.2019
https://doi.org/10.33808/clinexphealthsci.613963

Abstract

Project Number

113S083

References

  • 1. Skolnick P, Legutko B, Li X, Bymaster FP. Current perspectives on the development of non-biogenic amine-based antidepressants. Pharmacol Res 2001; 43(5): 411-23.
  • 2. Kulkarni SK and Dhir A. Current investigational drugs for major depression, Expert Opin Investig Drugs 2009; 18(6): 767-88.
  • 3. Lee TS, Quek SY and Krishnan KR. Molecular Imaging for Depressive Disorders, AJNR Am J Neuroradiol 2014; 35(6): 44-54.
  • 4. Arciniegas DB, Anderson CA, Topkoff J, McAllister TW. Mild traumatic brain injury: a neuropsychiatric approach to diagnosis, evaluation, and treatment, Neuropsychiatr Dis Treat 2005; 1(4): 311–327.
  • 5. Duman RS. Pathophysiology of depression and innovative treatments: remodelling glutamatergic synaptic connections, Dialogues in Clinical neuroscience 2014; 16: 11-27.
  • 6. Zhu X, Ye G, Wang Z , Luo J, Hao X. Sub-anesthetic doses of ketamine exert antidepressant-like effects and upregulate the expression of glutamate transporters in the hippocampus of rats, Neuroscience Letters 2017; 639(3): 132–137.
  • 7. Czéh B, Fuchs E, Wiborg O, Simong M. Animal models of major depression and their clinical implications, Progress in Neuro-Psychopharmacology and Biological Psychiatry 2016; 64: 293-310.
  • 8. Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation, Psychopharmacology 1997; 134(4): 319–329.
  • 9. Willner P. Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS, Neuropsychobiology 2005; 52: 90–110.
  • 10. Willner et al., Chronic mild stress-induced anhedonia: A realistic animal model of depression, Neuroscience & Biobehavioral Reviews 1992; 16 (4): 525-534.
  • 11. Helena M. Abelaira HM, Reus GZ, Quevedo J. Animal models as tools to study the pathophysiology of depression, Rev Bras Psiquiatr 2013; 35(2): 112-120.
  • 12. Deussing JM. Animal models of depression, Drug Discovery Today: Disease Models 2006; 3(4): 375-383.
  • 13. Wiborg O. Chronic mild stress for modeling anhedonia, Cell and Tissue Research 2013; 354(1): 155–169.
  • 14. Haapakoski R, Ebmeier KP, Aleniusc H,Kivimäki M. Innate and adaptive immunity in the development of depression: An update on current knowledge and technological advances, Progress in Neuro-Psychopharmacology and Biological Psychiatry 2016; 66: 63-72.
  • 15. Kaufmann FN, Costa AP, Ghisleni G, Diaz AP, Rodrigues ALS, Peluffo H, Kaster MP. NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings, Brain Behav Immun. 2017; 64: 367-383.
  • 16. Valtcheva S and Venance L. Astrocytes gate Hebbian synaptic plasticity in the striatum, Nat Commun 2016; 20(7): 1-17.
  • 17. Willner P, Towell A, Sampson D, Sophokleous S, Muscat R. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant, Psychopharmacology 1987; 93(3): 358-364.
  • 18. Yazir Y, Utkan T, and Aricioglu F. Inhibition of neuronal nitric oxide synthase and soluble guanylate cyclase prevents depression-like behaviour in rats exposed to chronic unpredictable mild stres, Basic Clin Pharmacol Toxicol 2012; 111(3): 154-60.
  • 19. Jiang P, Zhang WY, Li HD, Cai HL, Liu YP, Chen LY. Stress and vitamin D: altered vitamin D metabolism in both the hippocampus and myocardium of chronic unpredictable mild stress exposed rats, Psychoneuroendocrinology 2013; 38(10): 2091-2098.
  • 20. Nollet M, Le Guisquet AM, Belzung C. Models of depression: unpredictable chronic mild stress in mice, Curr Protoc Pharmacol. 2013; 5: 5.
  • 21. Burmeister J, Kota C, Maughan RL, Spokas JJ, Coderre JA, Ma R, Wielopolski L. A conducting plastic simulating brain tissue, Med Phys 2000; 27(11): 2560-2564.
  • 22. Hacimuftuoglu A, Tatar A, Cetin D, Taspinar N, Saruhan F, Okkay U, Turkez H, Unal D, Stephens RL Jr, Suleyman H. Astrocyte/neuron ratio and its importance on glutamate toxicity: an in vitro voltammetric study, Cytotechnology 2016; 68(4): 1425-1433.
  • 23. Mitani H, Shirayama Y, Yamada T, Maeda K, Ashby CR, Kawahara R. Correlation between plasma levels of glutamate, alanine and serine with severity of depression, Progress in Neuro-Psychopharmacology & Biological Psychiatry 2006; 30: 1155-1158.
  • 24. Rothstein JD, Kammen VM, Levey AI, Martin LJ, Kuncl RW. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis, Annals of Neurology 1995; 38: 73-84.
  • 25. Stephens RL. Glutamate transporter activators as anti-nociceptive agents, The Eurasian Journal of Medicine 2011; 43: 182-185.
  • 26. Jaquins-Gerstl A and Michael AC. Comparison of the brain penetration injury associated with microdialysis and voltammetry, journal of neurosciences methods 2009; 183(2): 127-135.
  • 27. Medina A, Burke S, Thompson RC, Bunney W, Myers RM, Schatzberg A, Akil H, Watson SJ. Glutamate transporters: a key piece in the glutamate puzzle of major depressive disorder, Journal of Psychiatric Research 2013; 47: 1150-1156.
  • 28. Kim K, Seok-Guen L, Kegelman TP, Su ZZ, Das SK, Dash R, Dasgupta S, Barral PM, Hedvat M, PAUL Diaz P, Reed JC, Stebbins JL, Pellecchia M, Sarkar D, Fisher PB. Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics, J Cell Physiol 2011; 226(10): 2484-93.
  • 29. Tower DB and OM Young. The activities of butyrylcholinesterase and carbonic anhydrase, the rate of anaerobic glycolysis, and the question of a constant density of glial cells in cerebral cortices of various mammalian species from mouse to whale, J Neurochem 1973; 20(2): 269-78.
  • 30. Medina A, Burke S, Thompson RC, Bunney W, Myers RM, Schatzberg A, Akil H, Watson SJ. Glutamate transporters: a key piece in the glutamate puzzle of major depressive disorder. Journal of Psychiatric Researc 2013; 47: 1150-1156.
  • 31. Tordera RM, Garcia-Garcia AL, Elizalde N, Segura V, Aso E, Venzala E, Ramirez MJ, Del Rio J. Chronic stress and impaired glutamate function elicit a depressive-like phenotype and common changes in gene expression in the mouse frontal cortex. European Neuropsychopharmacology 2011; 21: 23-32.
  • 32. Yang H, Spence JS, Devous MD, Briggs RW, Goyal A, Xiao H, Yadav H, Adinoff B. Striatal-limbic activation is associated with intensity of anticipatory anxiety, Psychiatry Research 2012; 204: 123-131.
There are 32 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Damla Binnetoğlu 0000-0002-7041-7253

Feyza Arıcıoglu 0000-0003-4669-9382

Halil Ozcan 0000-0001-7412-7774

Ufuk Okkay This is me 0000-0002-2871-0712

Ahmet Hacımuftuoglu 0000-0002-9658-3313

Project Number 113S083
Publication Date December 31, 2019
Submission Date September 1, 2019
Published in Issue Year 2019 Volume: 9 Issue: 4

Cite

APA Binnetoğlu, D., Arıcıoglu, F., Ozcan, H., Okkay, U., et al. (2019). Antidepressant-Like Effects of Ceftriaxone in Chronic Unpredictable Mild Stress Model in Rats: The Importance of Reuptake Time of Glutamate. Clinical and Experimental Health Sciences, 9(4), 294-299. https://doi.org/10.33808/clinexphealthsci.613963
AMA Binnetoğlu D, Arıcıoglu F, Ozcan H, Okkay U, Hacımuftuoglu A. Antidepressant-Like Effects of Ceftriaxone in Chronic Unpredictable Mild Stress Model in Rats: The Importance of Reuptake Time of Glutamate. Clinical and Experimental Health Sciences. December 2019;9(4):294-299. doi:10.33808/clinexphealthsci.613963
Chicago Binnetoğlu, Damla, Feyza Arıcıoglu, Halil Ozcan, Ufuk Okkay, and Ahmet Hacımuftuoglu. “Antidepressant-Like Effects of Ceftriaxone in Chronic Unpredictable Mild Stress Model in Rats: The Importance of Reuptake Time of Glutamate”. Clinical and Experimental Health Sciences 9, no. 4 (December 2019): 294-99. https://doi.org/10.33808/clinexphealthsci.613963.
EndNote Binnetoğlu D, Arıcıoglu F, Ozcan H, Okkay U, Hacımuftuoglu A (December 1, 2019) Antidepressant-Like Effects of Ceftriaxone in Chronic Unpredictable Mild Stress Model in Rats: The Importance of Reuptake Time of Glutamate. Clinical and Experimental Health Sciences 9 4 294–299.
IEEE D. Binnetoğlu, F. Arıcıoglu, H. Ozcan, U. Okkay, and A. Hacımuftuoglu, “Antidepressant-Like Effects of Ceftriaxone in Chronic Unpredictable Mild Stress Model in Rats: The Importance of Reuptake Time of Glutamate”, Clinical and Experimental Health Sciences, vol. 9, no. 4, pp. 294–299, 2019, doi: 10.33808/clinexphealthsci.613963.
ISNAD Binnetoğlu, Damla et al. “Antidepressant-Like Effects of Ceftriaxone in Chronic Unpredictable Mild Stress Model in Rats: The Importance of Reuptake Time of Glutamate”. Clinical and Experimental Health Sciences 9/4 (December 2019), 294-299. https://doi.org/10.33808/clinexphealthsci.613963.
JAMA Binnetoğlu D, Arıcıoglu F, Ozcan H, Okkay U, Hacımuftuoglu A. Antidepressant-Like Effects of Ceftriaxone in Chronic Unpredictable Mild Stress Model in Rats: The Importance of Reuptake Time of Glutamate. Clinical and Experimental Health Sciences. 2019;9:294–299.
MLA Binnetoğlu, Damla et al. “Antidepressant-Like Effects of Ceftriaxone in Chronic Unpredictable Mild Stress Model in Rats: The Importance of Reuptake Time of Glutamate”. Clinical and Experimental Health Sciences, vol. 9, no. 4, 2019, pp. 294-9, doi:10.33808/clinexphealthsci.613963.
Vancouver Binnetoğlu D, Arıcıoglu F, Ozcan H, Okkay U, Hacımuftuoglu A. Antidepressant-Like Effects of Ceftriaxone in Chronic Unpredictable Mild Stress Model in Rats: The Importance of Reuptake Time of Glutamate. Clinical and Experimental Health Sciences. 2019;9(4):294-9.

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