EFFECTS OF 5HT1 AGONISTS AND ANTAGONISTS ON BRAIN TNF ALPHA AND IL1 - BETA LEVELS IN THE PENTYLENETETRAZOLE KINDLING MODEL EPILEPSY

Abstract

Objective(s): Epilepsy is a brain dysfunction characterized by neuronal hyperexcitability and synchronized electrical discharges that cause seizures to occur. Many other neurotransmitter systems such as Serotonin (5-hydroxytryptamine, 5-HT), dopamine (DA) and adrenaline are known to be involved in the mechanism of epileptogenesis. Neuroinflammation, oxidative stress, and mitochondrial dysfunction play an important role in explaining the pathophysiology of epilepsy. Inflammatory cytokine signals in the brain regulate important brain functions such as neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, dopaminergic transmission, and also affect neurogenesis. This study aimed to investigate the effect of serotonin 5HT-1 agonists and antagonists on TNF-alpha (tumor necrosis factor-alpha) and IL-1 beta (interleukin-1 beta) markers in PTZ (Pentylentetrazol)-Kindling model epileptic rats. Materials and Methods: Twenty-four male Wistar albino rats of 240-280gr were used in our study. PTZ injections were done on rats on Mondays, Wednesdays, and Fridays at a dose of 35 mg/kg to create PTZ kindling model epilepsy, then, on the days of injection, the animals' behavior was observed for 30 minutes, and the stages of epilepsy were determined according to the Racine seizure stages. The animals were then divided into four groups in a randomized way: Control (n = 8) 1ml/ kg SF, 35 mg/ kg PTZ (n = 8), 0.3 mg/ kg 8-OH-DPAT (n = 8) and 1 mg/kg WAY-100135 (n = 8), which were intraperitoneal administered. After the procedure, brain tissues were dissected from the animals. Data analyses were done with SPSS for Windows version 21.0 and evaluated using one-way variance analysis (ANOVA). Results: Between the groups, IL1-β and TNF-alpha results were evaluated. The PTZ group did not change the level of IL1-β compared to the control group (p>0.05), however, there was no statistically significant difference in IL1-β levels between 8-OH-DPAT and WAY-100135 groups (p>0.05). Similarly, PTZ did not change the TNF-alpha level compared to the control group, and there was no statistical difference when 8-OH-DPAT, WAY-100135 groups were compared with the PTZ group (p>0.05). Conclusion: In PTZ kindling epilepsy, the treatments in the 8-OH-DPA (5HT-1 agonist) and WAY-100135 (5HT-1 antagonist) groups showed no effect at TNF-alpha and IL1-β levels, despite this, more studies are needed to investigate the new therapeutic approach to treat epilepsy.