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Article

Susceptibility to Pentylenetetrazole-Induced Seizures in Mice with Distinct Activity of the Endogenous Opioid System

by
Anna Ruszczak
1,
Piotr Poznański
2,3,
Anna Leśniak
4,
Marzena Łazarczyk
2,
Dominik Skiba
2,
Agata Nawrocka
2,
Kinga Gaweł
5,
Justyna Paszkiewicz
6,
Michel-Edwar Mickael
2 and
Mariusz Sacharczuk
2,4,*
1
Department of Small Animal Diseases with Clinic, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland
2
Department of Experimental Genomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Postępu 36A, 05-552 Jastrzębiec, Poland
3
Laboratory of Host-Microbiota Interactions, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland
4
Department of Pharmacotherapy and Pharmaceutical Care, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-697 Warsaw, Poland
5
Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland
6
Department of Health, John Paul II University of Applied Sciences in Biala Podlaska, Sidorska 95/97, 21-500 Biała Podlaska, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(13), 6978; https://doi.org/10.3390/ijms25136978
Submission received: 28 April 2024 / Revised: 19 June 2024 / Accepted: 22 June 2024 / Published: 26 June 2024
(This article belongs to the Section Molecular Biology)
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Abstract

Currently, pharmacotherapy provides successful seizure control in around 70% of patients with epilepsy; however, around 30% of cases are still resistant to available treatment. Therefore, effective anti-epileptic therapy still remains a challenge. In our study, we utilized two mouse lines selected for low (LA) and high (HA) endogenous opioid system activity to investigate the relationship between down- or upregulation of the opioid system and susceptibility to seizures. Pentylenetetrazole (PTZ) is a compound commonly used for kindling of generalized tonic-clonic convulsions in animal models. Our experiments revealed that in the LA mice, PTZ produced seizures of greater intensity and shorter latency than in HA mice. This observation suggests that proper opioid system tone is crucial for preventing the onset of generalized tonic-clonic seizures. Moreover, a combination of an opioid receptor antagonist—naloxone—and a GABA receptor agonist—diazepam (DZP)—facilitates a significant DZP-sparing effect. This is particularly important for the pharmacotherapy of neurological patients, since benzodiazepines display high addiction risk. In conclusion, our study shows a meaningful, protective role of the endogenous opioid system in the prevention of epileptic seizures and that disturbances in that balance may facilitate seizure occurrence.
Keywords: seizures; epilepsy; endogenous opioid system seizures; epilepsy; endogenous opioid system

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MDPI and ACS Style

Ruszczak, A.; Poznański, P.; Leśniak, A.; Łazarczyk, M.; Skiba, D.; Nawrocka, A.; Gaweł, K.; Paszkiewicz, J.; Mickael, M.-E.; Sacharczuk, M. Susceptibility to Pentylenetetrazole-Induced Seizures in Mice with Distinct Activity of the Endogenous Opioid System. Int. J. Mol. Sci. 2024, 25, 6978. https://doi.org/10.3390/ijms25136978

AMA Style

Ruszczak A, Poznański P, Leśniak A, Łazarczyk M, Skiba D, Nawrocka A, Gaweł K, Paszkiewicz J, Mickael M-E, Sacharczuk M. Susceptibility to Pentylenetetrazole-Induced Seizures in Mice with Distinct Activity of the Endogenous Opioid System. International Journal of Molecular Sciences. 2024; 25(13):6978. https://doi.org/10.3390/ijms25136978

Chicago/Turabian Style

Ruszczak, Anna, Piotr Poznański, Anna Leśniak, Marzena Łazarczyk, Dominik Skiba, Agata Nawrocka, Kinga Gaweł, Justyna Paszkiewicz, Michel-Edwar Mickael, and Mariusz Sacharczuk. 2024. "Susceptibility to Pentylenetetrazole-Induced Seizures in Mice with Distinct Activity of the Endogenous Opioid System" International Journal of Molecular Sciences 25, no. 13: 6978. https://doi.org/10.3390/ijms25136978

APA Style

Ruszczak, A., Poznański, P., Leśniak, A., Łazarczyk, M., Skiba, D., Nawrocka, A., Gaweł, K., Paszkiewicz, J., Mickael, M.-E., & Sacharczuk, M. (2024). Susceptibility to Pentylenetetrazole-Induced Seizures in Mice with Distinct Activity of the Endogenous Opioid System. International Journal of Molecular Sciences, 25(13), 6978. https://doi.org/10.3390/ijms25136978

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