Skip to main content
SpringerLink
Log in

The effect of valproate on the amino acids, monoamines, and kynurenic acid concentrations in brain structures involved in epileptogenesis in the pentylenetetrazol-kindled rats

  • Article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Background

The study aimed to assess the influence of a single valproate (VPA) administration on inhibitory and excitatory neurotransmitter concentrations in the brain structures involved in epileptogenesis in pentylenetetrazol (PTZ)-kindled rats.

Methods

Adult, male Wistar rats were kindled by repeated intraperitoneal (ip) injections of PTZ at a subconvulsive dose (30 mg/kg, three times a week). Due to the different times required to kindle the rats (18–22 injections of PTZ), a booster dose of PTZ was administrated 7 days after the last rats were kindled. Then rats were divided into two groups: acute administration of VPA (400 mg/kg) or saline given ip. The concentration of amino acids, kynurenic acid (KYNA), monoamines, and their metabolites in the prefrontal cortex, hippocampus, amygdala, and striatum was assessed by high-pressure liquid chromatography (HPLC).

Results

It was found that a single administration of VPA increased the gamma-aminobutyric acid (GABA), tryptophan (TRP), 5-hydroxyindoleacetic acid (5-HIAA), and KYNA concentrations and decreased aspartate (ASP) levels in PTZ-kindled rats in the prefrontal cortex, hippocampus, amygdala and striatum.

Conclusions

Our results indicate that a single administration of VPA in the PTZ-kindled rats restored proper balance between excitatory (decreasing the level of ASP) and inhibitory neurotransmission (increased concentration GABA, KYNA) and affecting serotoninergic neurotransmission in the prefrontal cortex, hippocampus, amygdala, and striatum.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

3-MT:

3-Methoxytyramine

5-HIAA:

5-Hydroxyindoleacetic acid

5-HT:

Serotonin

ALA:

Alanine

ASP:

Aspartate

DA:

Dopamine

DOPAC:

3,4-Dihydroxyphenylacetic acid

GABA:

Gamma-aminobutyric acid

GABA-A:

Gamma-aminobutyric acid type A

GLU:

Glutamate

GLN:

Glutamine

GLY:

Glycine

HPLC:

High-pressure liquid chromatography

HVA:

Homovanillic acid

ip :

Intraperitoneal

KYNA:

Kynurenic acid

NA:

Noradrenaline

NMDA:

N-Methyl-D-aspartate

PTZ:

Pentylenetetrazol

SEM:

Standard error of the mean

TAU:

Taurine

TRP:

Tryptophan

VPA:

Valproate

References

  1. Geraghty JR, Senador D, Maharathi B, Butler MP, Sudhakar D, Smith RA, et al. Modulation of locomotor behaviors by location-specific epileptic spiking and seizures. Epilepsy Behav. 2021;114(Pt A): 107652. https://doi.org/10.1016/j.yebeh.2020.107652.

    Article  PubMed  Google Scholar 

  2. Pack AM. Epilepsy overview and revised classification of seizures and epilepsies. Continuum (Minneap Minn). 2019;25(2):306–21. https://doi.org/10.1212/CON.0000000000000707.

    Article  PubMed  Google Scholar 

  3. Engelborghs S, D’Hooge R, Deyn PPD. Pathophysiology of epilepsy. Acta Neurol Belg. 2000;100(4):201–13.

    CAS  PubMed  Google Scholar 

  4. Dhir A. Pentylenetetrazol (PTZ) kindling model of epilepsy. Curr Protoc Neurosci. 2012. https://doi.org/10.1002/0471142301.ns0937s58.

    Article  PubMed  Google Scholar 

  5. White HS. Clinical significance of animal seizure models and mechanism of action studies of potential antiepileptic drugs. Epilepsia. 1997;38(Suppl 1):S9-17. https://doi.org/10.1111/j.1528-1157.1997.tb04523.x.

    Article  CAS  PubMed  Google Scholar 

  6. Yuskaitis CJ, Rossitto LA, Groff KJ, Dhamne SC, Zhang B, Lalani LK, et al. Factors influencing the acute pentylenetetrazole-induced seizure paradigm and a literature review. Ann Clin Transl Neurol. 2021;8(7):1388–97. https://doi.org/10.1002/acn3.51375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Morimoto K, Fahnestock M, Racine RJ. Kindling and status epilepticus models of epilepsy: rewiring the brain. Prog Neurobiol. 2004;73:1–60.

    Article  CAS  PubMed  Google Scholar 

  8. Erum JV, Dam DV, Deyn PPD. PTZ-induced seizures in mice require a revised Racine scale. Epilepsy Behav. 2019;95:51–5.

    Article  PubMed  Google Scholar 

  9. Singh T, Mishra A, Goel RK. PTZ kindling model for epileptogenesis, refractory epilepsy, and associated comorbidities: relevance and reliability. Metab Brain Dis. 2021;36(7):1573–90. https://doi.org/10.1007/s11011-021-00823-3.

    Article  CAS  PubMed  Google Scholar 

  10. Ahmadi M, Dufour JP, Seifritz E, Mirnajafi-Zadeh J, Saab BJ. The PTZ kindling mouse model of epilepsy exhibits exploratory drive deficits and aberrant activity amongst VTA dopamine neurons in both familiar and novel space. Behav Brain Res. 2017;14(330):1–7. https://doi.org/10.1016/j.bbr.2017.05.025. (Epub 2017 May 12 PMID: 28506618).

    Article  CAS  Google Scholar 

  11. Davis R, Peters DH, McTavish D. Valproic acid. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy. Drugs. 1994;47(2):332–72 (PMID: 7512905).

    Article  CAS  PubMed  Google Scholar 

  12. Kessler SK, McGinnis E. A practical guide to treatment of childhood absence epilepsy. Paediatr Drugs. 2019;21(1):15–24. https://doi.org/10.1007/s40272-019-00325-x.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Tomson T, Battino D, Perucca E. Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honoured drug. Lancet Neurol. 2016;15(2):210–8. https://doi.org/10.1016/S1474-4422(15)00314-2.

    Article  CAS  PubMed  Google Scholar 

  14. Romoli M, Mazzocchetti P, D’Alonzo R, Siliquini S, Rinaldi VE, Verrotti A, Calabresi P, Costa C. Valproic acid and epilepsy: from molecular mechanisms to clinical evidences. Curr Neuropharmacol. 2019;17(10):926–46. https://doi.org/10.2174/1570159X17666181227165722.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Litvinova SA, Voronina TA, Kondrakhin EA, Gaydukov IO, Davletshin AI, Vasileva EV, et al. ERK1/2 kinases and dopamine D2 receptors participate in the anticonvulsant effects of a new derivative of benzoylpyridine oxime and valproic acid. Eur J Pharmacol. 2021;903: 174150. https://doi.org/10.1016/j.ejphar.2021.174150. (Epub 2021 May 5 PMID: 33961874).

    Article  CAS  PubMed  Google Scholar 

  16. Miziak B, Konarzewska A, Ułamek-Kozioł M, Dudra-Jastrzębska M, Pluta R, Czuczwar SJ. Anti-epileptogenic effects of antiepileptic drugs. Int J Mol Sci. 2020;21(7):2340. https://doi.org/10.3390/ijms21072340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Basselin M, Chang L, Chen M, Bell JM, Rapoport SI. Chronic administration of valproic acid reduces brain NMDA signaling via arachidonic acid in unanesthetized rats. Neurochem Res. 2008;33(11):2229–40. https://doi.org/10.1007/s11064-008-9700-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Davies JA. Mechanisms of action of antiepileptic drugs. Seizure. 1995;4:267–71. https://doi.org/10.1016/s1059-1311(95)80003-4.

    Article  CAS  PubMed  Google Scholar 

  19. Nau H, Löscher W. Valproic acid: brain and plasma levels of the drug and its metabolites, anticonvulsant effects and gamma-aminobutyric acid (GABA) metabolism in the mouse. J Pharmacol Exp Ther. 1982;220(3):654–9.

    CAS  PubMed  Google Scholar 

  20. Tunnicliff G. Actions of sodium valproate on the central nervous system. J Physiol Pharmacol. 1999;50(3):347–65.

    CAS  PubMed  Google Scholar 

  21. Maciejak P, Szyndler J, Turzyńska D, Sobolewska A, Płaźnik A. Kynurenic acid: a new effector of valproate action? Pharmacol Rep. 2011;63(6):1569–73. https://doi.org/10.1016/s1734-1140(11)70723-x.

    Article  CAS  PubMed  Google Scholar 

  22. Maciejak P, Szyndler J, Turzyńska D, Sobolewska A, Kołosowska K, Lehner M, et al. The kynurenine pathway: a missing piece in the puzzle of valproate action? Neuroscience. 2013;234:135–45. https://doi.org/10.1016/j.neuroscience.2012.12.052.

    Article  CAS  PubMed  Google Scholar 

  23. Maciejak P, Szyndler J, Kołosowska K, Turzyńska D, Sobolewska A, Walkowiak J, et al. Valproate disturbs the balance between branched and aromatic amino acids in rats. Neurotox Res. 2014;25(4):358–68. https://doi.org/10.1007/s12640-013-9441-0.

    Article  CAS  PubMed  Google Scholar 

  24. Maciejak P, Szyndler J, Turzyńska D, Sobolewska A, Bidziński A, Kołosowska K, et al. Time course of changes in the concentration of amino acid in the brain structures of pentyleneterazole-kindled rats. Brain Res. 2010;1342:150–9. https://doi.org/10.1016/j.brainres.2010.04.045.

    Article  CAS  PubMed  Google Scholar 

  25. Joshi D, Katyal J, Arava S, Gupta YK. Effects of enalapril and losartan alone and in combination with sodium valproate on seizures, memory, and cardiac changes in rats. Epilepsy Behav. 2019;92:345–52. https://doi.org/10.1016/j.yebeh.2018.12.019.

    Article  PubMed  Google Scholar 

  26. Kołosowska K, Maciejak P, Szyndler J, Turzyńska D, Sobolewska A, Płaźnik A. The role of interleukin-1β in the pentylenetetrazole-induced kindling of seizures, in the rat hippocampus. Eur J Pharmacol. 2014;731:31–7. https://doi.org/10.1016/j.ejphar.2014.03.008.

    Article  CAS  PubMed  Google Scholar 

  27. Töllner K, Twele F, Löscher W. Evaluation of the pentylenetetrazole seizure threshold test in epileptic mice as surrogate model for drug testing against pharmacoresistant seizures. Epilepsy Behav. 2016;57(Pt A):95–104. https://doi.org/10.1016/j.yebeh.2016.01.032.

    Article  PubMed  Google Scholar 

  28. Szyndler J, Maciejak P, Turzyńska D, Sobolewska A, Bidziński A, Płaźnik A. Time course of changes in the concentrates of monoamines in the brain structures of pentylenetetrazole-kindled rats. J Neural Transm. 2010;117:707–18. https://doi.org/10.1007/s00702-010-0414-7.

    Article  PubMed  Google Scholar 

  29. Wlaź P, Ebert U, Potschka H, Löscher W. Electrical but not chemical kindling increases sensitivity to some phencyclidine-like behavioral effects induced by the competitive NMDA receptor antagonist D-CPPene in rats. Eur J Pharmacol. 1998;353(2–3):177–89. https://doi.org/10.1016/s0014-2999(98)00409-9.

    Article  PubMed  Google Scholar 

  30. Paxinos G, Watson CH. The rat brain in stereotaxic coordinates. 4th ed. San Diego: Academic Press; 1998.

    Google Scholar 

  31. Szyndler J, Maciejak P, Turzyńska D, Sobolewska A, Walkowiak J, Płaźnik A. The effects of electrical hippocampal kindling of seizures on amino acids and kynurenic acid concentrations in brain structures. J Neural Transm. 2012;119:141–9. https://doi.org/10.1007/s00702-011-0700-z.

    Article  CAS  PubMed  Google Scholar 

  32. Rowley HL, Martin KF, Marsden CA. Determination of in vivo amino acid neurotransmitters by high-performance liquid chromatography with o-phthalaldehyde-sulphite derivatisation. J Neurosci Methods. 1995;57(1):93–9. https://doi.org/10.1016/0165-0270(94)00132-z.

    Article  CAS  PubMed  Google Scholar 

  33. Wu HQ, Monno A, Schwarcz R, Vezzani A. Electrical kindling is associated with a lasting increase in the extracellular levels of kynurenic acid in the rat hippocampus. Neurosci Lett. 1995;198(2):91–4. https://doi.org/10.1016/0304-3940(95)11971-x.

    Article  CAS  PubMed  Google Scholar 

  34. Hervé C, Beyne P, Jamault H, Delacoux E. Determination of tryptophan and its kynurenine pathway metabolites in human serum by high-performance liquid chromatography with simultaneous ultraviolet and fluorimetric detection. J Chromatogr B Biomed Appl. 1996;675(1):157–61. https://doi.org/10.1016/0378-4347(95)00341-x.

    Article  PubMed  Google Scholar 

  35. Kaneda N, Asano M, Nagatsu T. Simple method for the simultaneous determination of acetylcholine, choline, noradrenaline, dopamine and serotonin in brain tissue by high-performance liquid chromatography with electrochemical detection. J Chromatogr. 1986;360(1):211–8. https://doi.org/10.1016/s0021-9673(00)91664-9.

    Article  CAS  PubMed  Google Scholar 

  36. Deng Y, Wang M, Wang W, Ma C, He N. Comparison and effects of acute lamotrigine treatment on extracellular excitatory amino acids in the hippocampus of PTZ-kindled epileptic and PTZ-induced status epilepticus rats. Neurochem Res. 2013;38(3):504–11. https://doi.org/10.1007/s11064-012-0942-7.

    Article  CAS  PubMed  Google Scholar 

  37. Flores-Soto M, Romero-Guerrero C, Vázquez-Hernández N, Tejeda-Martínez A, Martín-Amaya-Barajas FL, et al. Pentylenetetrazol-induced seizures in adult rats are associated with plastic, changes to the dendritic spines on hippocampal CA1 pyramidal neurons. Behav Brain Res. 2021;406: 113198. https://doi.org/10.1016/j.bbr.2021.113198.

    Article  CAS  PubMed  Google Scholar 

  38. Ciltas AC, Toy CE, Güneş H, Yaprak M. Effects of probiotics on GABA/glutamate and oxidative stress in PTZ- induced acute seizure model in rats. Epilepsy Res. 2023;195: 107190. https://doi.org/10.1016/j.eplepsyres.2023.107190.

    Article  CAS  PubMed  Google Scholar 

  39. Li ZP, Zhang XY, Lu X, Zhong MK, Ji YH. Dynamic release of amino acid transmitters induced by valproate in PTZ-kindled epileptic rat hippocampus. Neurochem Int. 2004;44(4):263–70. https://doi.org/10.1016/s0197-0186(03)00148-7.

    Article  CAS  PubMed  Google Scholar 

  40. Lasoń W, Chlebicka M, Rejdak K. Research advances in basic mechanisms of seizures and antiepileptic drug action. Pharmacol Rep. 2013;65(4):787–801. https://doi.org/10.1016/s1734-1140(13)71060-0.

    Article  PubMed  Google Scholar 

  41. Maciejak P, Szyndler J, Turzyńska D, Sobolewska A, Taracha E, Skórzewska A, et al. Time course of changes in the concentration of kynurenic acid in the brain of pentylenetetrazol-kindled rats. Brain Res Bull. 2009;78(6):299–305. https://doi.org/10.1016/j.brainresbull.2008.10.010.

    Article  CAS  PubMed  Google Scholar 

  42. Szyndler J, Maciejak P, Turzyńska D, Sobolewska A, Taracha E, Skórzewska A, et al. Mapping of c-Fos expression in the rat brain during the evolution of pentylenetetrazol-kindled seizures. Epilepsy Behav. 2009;16(2):216–24. https://doi.org/10.1016/j.yebeh.2009.07.030.

    Article  PubMed  Google Scholar 

  43. Nieoczym D, Socała K, Zelek-Molik A, Pieróg M, Przejczowska-Pomierny K, Szafarz M, et al. Anticonvulsant effect of pterostilbene and its influence on the anxiety- and depression-like behavior in the pentetrazol-kindled mice: behavioral, biochemical, and molecular studies. Psychopharmacology. 2021;238(11):3167–81. https://doi.org/10.1007/s00213-021-05933-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sendrowski K, Sobaniec W. Hippocampus, hippocampal sclerosis and epilepsy. Pharmacol Rep. 2013;65(3):555–65. https://doi.org/10.1016/s1734-1140(13)71033-8.

    Article  CAS  PubMed  Google Scholar 

  45. Sierra A, Gröhn O, Pitkänen A. Imaging microstructural damage and plasticity in the hippocampus during epileptogenesis. Neuroscience. 2015;19(309):162–72. https://doi.org/10.1016/j.neuroscience.2015.04.054.

    Article  CAS  Google Scholar 

  46. Engel J Jr. Epileptogenesis, traumatic brain injury, and biomarkers. Neurobiol Dis. 2019;123:3–7. https://doi.org/10.1016/j.nbd.2018.04.002.

    Article  CAS  PubMed  Google Scholar 

  47. Li L, He L, Harris N, Zhou Y, Engel J Jr, Bragin A. Topographical reorganization of brain functional connectivity during an early period of epileptogenesis. Epilepsia. 2021;62(5):1231–43. https://doi.org/10.1111/epi.16863.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Aroniadou-Anderjaska V, Fritsch B, Qashu F, Braga MF. Pathology and pathophysiology of the amygdala in epileptogenesis and epilepsy. Epilepsy Res. 2008;78(2–3):102–16. https://doi.org/10.1016/j.eplepsyres.2007.11.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. de Souza AG, Chaves Filho AJM, Souza Oliveira JV, de Souza DAA, Lopes IS, de Carvalho MAJ, et al. Prevention of pentylenetetrazole-induced kindling and behavioral comorbidities in mice by levetiracetam combined with the GLP-1 agonist liraglutide: involvement of brain antioxidant and BDNF upregulating properties. Biomed Pharmacother. 2019;109:429–39. https://doi.org/10.1016/j.biopha.2018.10.066. (Epub 2018 Nov 3 PMID: 30399578).

    Article  CAS  PubMed  Google Scholar 

  50. Tokudome K, Okumura T, Shimizu S, Mashimo T, Takizawa A, Serikawa T, et al. Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission. Sci Rep. 2016;6:27420. https://doi.org/10.1038/srep27420.PMID:27265781;PMCID:PMC4893657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Tchekalarova J, Sotiriou E, Angelatou F. Down-regulation of dopamine D1 and D2 receptors in the basal ganglia of PTZ kindling model of epilepsy: effects of angiotensin IV. Brain Res. 2004;1024(1–2):159–66. https://doi.org/10.1016/j.brainres.2004.07.060. (PMID: 15451378).

    Article  CAS  PubMed  Google Scholar 

  52. Yu Y, Xie W, Wang C. Chaihushugan decoction exerts antiepileptic effects by increasing hippocampal glutamate metabolism in pentylenetetrazole-kindled rats. J Tradit Chin Med. 2015;35(6):659–65. https://doi.org/10.1016/s0254-6272(15)30156-4.

    Article  PubMed  Google Scholar 

  53. Chapman AG, Hart GP. Anticonvulsant drug action and regional neurotransmitter amino acid changes. J Neural Transm. 1988;72(3):201–12. https://doi.org/10.1007/BF01243420.

    Article  CAS  PubMed  Google Scholar 

  54. Tamboli AM, Rub RA, Ghosh P, Bodhankar SL. Antiepileptic activity of lobeline isolated from the leaf of Lobelia nicotianaefolia and its effect on brain GABA level in mice. Asian Pac J Trop Biomed. 2012;2(7):537–42. https://doi.org/10.1016/S2221-1691(12)60092-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Nishikawa T, Yamamoto N, Tsuchida H, Umino A, Kawaguchi N. Endogenous D-serine in mammalian brains. Nihon Shinkei Seishin Yakurigaku Zasshi. 2000;20(1):33–9.

    CAS  PubMed  Google Scholar 

  56. Szyndler J, Maciejak P, Turzyńska D, Sobolewska A, Lehner M, Taracha E, et al. Changes in the concentration of amino acids in the hippocampus of pentylenetetrazole-kindled rats. Neurosci Lett. 2008;439(3):245–9. https://doi.org/10.1016/j.neulet.2008.05.002.

    Article  CAS  PubMed  Google Scholar 

  57. Maciejak P, Szyndler J, Turzyńska D, Sobolewska A, Kołosowska K, Krząścik P, et al. Is the interaction between fatty acids and tryptophan responsible for the efficacy of a ketogenic diet in epilepsy? The new hypothesis of action. Neuroscience. 2016;313:130–48. https://doi.org/10.1016/j.neuroscience.2015.11.029.

    Article  CAS  PubMed  Google Scholar 

  58. Jobe PC, Hem Ko KHL, Ray T, Dailey JW. Abnormalities in monoamine levels in the central nervous system in the genetically epilepsy-prone rats. Epilepsia. 1982;23:359–66. https://doi.org/10.1111/j.1528-1157.1982.tb05421.x.

    Article  CAS  PubMed  Google Scholar 

  59. Corcoran ME, Teskey GC. Chapter: models characteristic and mechanism of kindling. In: Schwartzkroin PA, editor. Encyclopedia of basic epilepsy research. 1st ed. Cambridge University Press.

  60. Reinhart CJ, McIntyre DC, Pellis SM, Kolb BE. Prefrontal neuronal morphology in kindling-prone (FAST) and kindling-resistant (SLOW) rats. Synapse. 2021;75(9): e22217. https://doi.org/10.1002/syn.22217.

    Article  CAS  PubMed  Google Scholar 

  61. Kücker S, Töllner K, Piechotta M, Gernert M. Kindling as a model of temporal lobe epilepsy induces bilateral changes in spontaneous striatal activity. Neurobiol Dis. 2010;37(3):661–72. https://doi.org/10.1016/j.nbd.2009.12.002.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The study was supported by Grant 2018/28/C/NZ7/00240 from the National Science Centre in Poland.

Author information

Authors and Affiliations

  1. Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Banacha 1B, 02-097, Warszawa, Poland

    Aleksandra Wisłowska-Stanek, Janusz Szyndler & Piotr Maciejak

  2. Department of Experimental and Clinical Neuroscience, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957, Warszawa, Poland

    Danuta Turzyńska, Alicja Sobolewska, Karolina Kołosowska, Anna Skórzewska & Piotr Maciejak

Authors
  1. Aleksandra Wisłowska-Stanek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Danuta Turzyńska
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alicja Sobolewska
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karolina Kołosowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Janusz Szyndler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anna Skórzewska
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Piotr Maciejak
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Aleksandra Wisłowska-Stanek: conceptualization, formal analysis, original draft writing. Danuta Turzyńska: conceptualization, behavioral tests, HPLC analysis. Alicja Sobolewska: statistical analysis, HPLC analysis. Anna Skórzewska: statistical analysis, validation. Karolina Kołosowska: methodology, validation, writing—review and editing. Janusz Szyndler: conceptualization, writing—review and editing. Piotr Maciejak: methodology, data analysis, writing—review and editing.

Corresponding author

Correspondence to Aleksandra Wisłowska-Stanek.

Ethics declarations

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical approval

The study was approved by the Committee for Animal Care and Use at the Medical University in Warsaw (Consent number 29/2010) and was consistent with the European Communities Council Directive (2010/63/EU).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wisłowska-Stanek, A., Turzyńska, D., Sobolewska, A. et al. The effect of valproate on the amino acids, monoamines, and kynurenic acid concentrations in brain structures involved in epileptogenesis in the pentylenetetrazol-kindled rats. Pharmacol. Rep 76, 348–367 (2024). https://doi.org/10.1007/s43440-024-00573-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43440-024-00573-w

Keywords

Search

Navigation