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The Role of 5-HT1A Receptors and Neuronal Nitric Oxide Synthase in a Seizur Induced Kindling Model in Rats

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Abstract

Background and Objective

Dentate gyrus (DG) has a high density of 5-HT1A receptors. It has neural nitric oxide synthase (nNOS), which is involved in neural excitability. The purpose of this study was to investigate the role of 5-HT1A receptors and nNOS of DG in perforant path kindling model of epilepsy.

Material and Methods

To achieve this purpose, a receptor antagonist (WAY100635, 0.1 mg/kg, intracerebroventricular, i.c.v) and neuronal nitric oxide synthase inhibitor (7-NI, 15 mg/kg, intraperitoneal, i.p.) were injected during kindling aquisition. Adult male Wistar rats (280 ± 20 g) were used in this study Animals were kindled through the daily administration of brief electrical stimulations (10 stimulations per day) to the perforant pathway. Field potential recordings were performed for 20 min in DG beforehand. Additionally, glial fibrillary acidic protein (GFAP) expression rate in the DG was determined using immunohistochemistry as a highly specific marker for glia.

Results

WAY100635 (0.1 mg/kg) significantly attenuated the kindling threshold compared to the kindled + vehicle group (P < 0.001). The co-administration of WAY100635 with 7-NI, exerted a significant anticonvulsive effect. Furthermore, the slope of field Excitatory Post Synaptic Potentials (fEPSP) at the end of 10 days in the kindled + 7-NI + WAY100635 group was significantly lower than in the kindled + vehicle group (P < 0.001). Furthermore, immunohistochemistry showed that the density of GAFP+ cells in the kindled + 7-NI + WAY100635 group was significantly higher than in the kindled + vehicle group (P < 0.001).

Conclusion

Our data demonstrate that antagonists of 5-HT1A receptors have proconvulsive effects and that astrocyte cells are involved in this process, while nNOS has an inhibitory effect on neuronal excitability.

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Authors and Affiliations

  1. Student Research Committee, Department of Physiology and Pharmacology, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Zinat Heydarnia Kalati

  2. Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Omid Gholami, Bahareh Amin & Akbar Pejhan

  3. Department of Physiology and Pharmacology, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Omid Gholami, Bahareh Amin & Akbar Pejhan

  4. Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Sajad Sahab-Negah

  5. Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran

    Masoumeh Gholami

  6. Department of Physiology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

    Hassan Azhdari-Zarmehri

  7. Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Mohammad-Zadeh

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  1. Zinat Heydarnia Kalati
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Correspondence to Hassan Azhdari-Zarmehri or Mohammad Mohammad-Zadeh.

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Kalati, Z.H., Gholami, O., Amin, B. et al. The Role of 5-HT1A Receptors and Neuronal Nitric Oxide Synthase in a Seizur Induced Kindling Model in Rats. Neurochem Res 47, 1934–1942 (2022). https://doi.org/10.1007/s11064-022-03577-1

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  • DOI: https://doi.org/10.1007/s11064-022-03577-1

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