Abstract
Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.
Highlights
Epilepsy is one of the most common neurological disorders and it is characterized by recurrent seizures
Drugs and reagents Pentylenetetrazole (PTZ), serotonin hydrochloride (5-HT), sumatriptan succinate, fluoxetine hydrochloride, cOmpleteTM protease inhibitor cocktail, and phosphate-buffered saline were purchased from Sigma-Aldrich (Schnelldorf, Germany); IL-1β, IL-6, and TNF-α ELISA kits were purchased from ELABscience
Sumatriptan pre-treatment had no effect on the onset time of the first myoclonic jerk compared with the NS+PTZ group (P=1.0, Figure 2A)
Summary
Epilepsy is one of the most common neurological disorders and it is characterized by recurrent seizures. Increasing evidence suggests that neuroinflammation, as a trigger for the seizures, is implicated in the pathophysiology of epilepsy[2,3,4]. Aberrational inflammatory processes such as long-lasting inflammation cause abnormal neural connectivity and hyperexcitability that result in the induction of epileptic seizures[5,6]. Serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin
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