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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2021; 67(1): 11-15


Mecamylamine modulates epileptiform discharges in low-Mg2+ model of epilepsy

O.S. Zapukhliak, D.S. Isaev

  1. Bogomoletz Institute of physiology NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz67.01.011

Abstract

Mecamylamine is a nonselective antagonist of nicotinic acetylcholine receptors that was developed as an antihypertensive medication and is now being studied for its beneficial effects in several pathological conditions, such as substance abuse, depression, anxiety and epilepsy. In this work, we investigate the effect of mecamylamine on the manifestations of seizure-like activity evoked by perfusion of hippocampal slices with low-Mg2+ solution of artificial cerebrospinal fluid. Reducing Mg2+ concentration in extracellular solution induced two distinct types of epileptiform activity: recurring seizure-like activity and continuous discharges. Application of mecamylamine significantly increased internal frequency of recurring seizurelike activity and significantly decreased inter-event intervals between continuous discharges. We also show that mecamylamine significantly decreased internal frequency of continuous epileptiform discharges. The results of our work show that mecamylamine exerts modulatory effect on the low-Mg2+ epileptiform activity induced in hippocampal acute rat brain slices. Additionally, obtained results indicate the role of nicotinic acetylcholine receptors in the modulation of hippocampal network activity, which might explain some of the therapeutic effects of mecamylamine in CNS.

Keywords: mecamylamine; rat brain slices; seizure-like activity; CA3 hippocampus

References

  1. Hasselmo ME. The role of acetylcholine in learning and memory. Current Opin Neurobiol. 2006 Dec 1;16(6):710-5. CrossRef PubMed PubMedCentral
  2. Matsuyama S, Matsumoto A, Enomoto T, Nishizaki T. Activation of nicotinic acetylcholine receptors induces long‐term potentiation in vivo in the intact mouse dentate gyrus. Eur J Neurosci. 2000 Oct;12(10):3741-7. CrossRef PubMed
  3. Picciotto MR, Caldarone BJ, King SL, Zachariou V. Nicotinic receptors in the brain: links between molecular biology and behavior. Neuropsychopharmacology. 2000 May 1;22(5):451-65. CrossRef
  4. Becchetti A, Aracri P, Meneghini S, Brusco S, Amadeo A. The role of nicotinic acetylcholine receptors in autosomal dominant nocturnal frontal lobe epilepsy. Front Physiol. 2015 Feb 11;6:22. CrossRef PubMed PubMedCentral
  5. Steinlein OK, Bertrand D. Nicotinic receptor channelopathies and epilepsy. Pflüg Arch-Eur J Physiol. 2010 Jul 1;460(2):495-503. CrossRef PubMed
  6. Iha HA, Kunisawa N, Shimizu S, Tokudome K, Mukai T, Kinboshi M, Ikeda A, Ito H, Serikawa T, Ohno Y. Nicotine elicits convulsive seizures by activating amygdalar neurons. Front Pharmacol. 2017 Feb 9;8:57. CrossRef PubMed PubMedCentral
  7. Löscher W, Potschka H, Wlaź P, Danysz W, Parsons CG. Are neuronal nicotinic receptors a target for antiepileptic drug development? Studies in different seizure models in mice and rats. Eur J Pharmacol. 2003 Apr 11;466(1- 2):99-111. CrossRef
  8. Nickell JR, Grinevich VP, Siripurapu KB, Smith AM, Dwoskin LP. Potential therapeutic uses of mecamylamine and its stereoisomers. Pharmac Biochem Behav. 2013 Jul 1;108:28-43. CrossRef PubMed PubMedCentral
  9. Bacher I, Wu B, Shytle DR, George TP. Mecamylamine-a nicotinic acetylcholine receptor antagonist with potential for the treatment of neuropsychiatric disorders. Exp Opin Pharmacother. 2009 Nov 1;10(16):2709-21. CrossRef PubMed
  10. Albus K, Wahab A, Heinemann U. Standard antiepileptic drugs fail to block epileptiform activity in rat organotypic hippocampal slice cultures. Br J Pharmacol. 2008 Jun;154(3):709-24. CrossRef PubMed PubMedCentral
  11. Coulter DA, Lee CJ. Thalamocortical rhythm generation in vitro: extra-and intracellular recordings in mouse thalamocortical slices perfused with low Mg2+ medium. Brain Res. 1993 Dec 17;631(1):137-42. CrossRef
  12. Sombati SO, Delorenzo RJ. Recurrent spontaneous seizure activity in hippocampal neuronal networks in culture. J Neurophysiol. 1995 Apr 1;73(4):1706-11. CrossRef PubMed
  13. Walther H, Lambert JD, Jones RS, Heinemann U, Hamon B. Epileptiform activity in combined slices of the hippocampus, subiculum and entorhinal cortex during perfusion with low magnesium medium. Neurosci Lett. 1986 Aug 29;69(2):156-61. CrossRef
  14. Nuytten D, Van Hees J, Meulemans A, Carton H. Magnesium deficiency as a cause of acute intractable seizures. J Neurol. 1991 Aug 1;238(5):262-4. CrossRef PubMed
  15. Borges LF, Giicer G. Effect of magnesium on epileptic foci. Epilepsia. 1978 Feb;19(1):81-91. CrossRef PubMed
  16. Duley L, Gülmezoglu AM, Henderson‐Smart DJ, Chou D. Magnesium sulphate and other anticonvulsants for women with pre‐eclampsia. Cochrane Database Systematic Reviews. 2010(11). CrossRef PubMed PubMedCentral
  17. Zapukhliak OS, Kachanovska VO, Isaeva EV, Netsyk OV, Isaev DS. Surface charge impact in nonsynaptic model of epilepsy in rat hippocampus. Fiziol Zh. 2016;62(2):35-40. Ukraine. CrossRef PubMed
  18. Isaev D, Ivanchick G, Khmyz V, Isaeva E, Savrasova A, Krishtal O, Holmes GL, Maximyuk O. Surface charge impact in low-magnesium model of seizure in rat hippocampus. J Neurophysiol. 2012 Jan;107(1):417-23. CrossRef PubMed PubMedCentral

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