Abstract
The entorhinal cortex (EC) plays a pivotal role in epileptogenesis and seizures. EC expresses high density of serotonergic receptors, especially 5-HT3 receptors. Cognitive impairment is common among people with epilepsy. The present study investigated the role of 5-HT3 receptor on the severity of seizures and learning and memory impairment by electrical kindling of amygdala in rats. The amygdala kindling was conducted in a chronic kindling manner in male Wistar rats. In fully kindled animals, ramosetron (as a potent and selective 5-HT3 receptor antagonist) was microinjected unilaterally (ad doses of 1, 10 or 100 µg/0.5 µl) into the EC 5 min before the novel object recognition (NOR) and Y-maze tests or kindling stimulations. Applying ramosetron at the concentration of 100 μg/0.5 µl (but not at 1 and 10 µg/0.5 µl) reduced afterdischarge (AD) duration and increased stage 4 latency in the kindled rats. Moreover, the obtained data from the NOR test showed that treatment by ramosetron (10 and 100 µg/0.5 µl) increased the discrimination index in the fully kindled animals. Microinjection of ramosetron (10 and 100 µg/0.5 µl) in fully kindled animals reversed the kindling induced changes in the percentage of spontaneous alternation in Y-maze task. The findings demonstrated an anticonvulsant role for a selective 5-HT3 receptor antagonist microinjected into the EC, therefore, suggesting an excitatory role for the EC 5-HT3 receptors in the amygdala kindling model of epilepsy. This anticonvulsive effect was accompanied with a restoring effect on cognitive behavior in NOR and Y-maze tests.
Highlights
Epilepsy is a chronic neurological disorder, with a prevalence of about 1%, which is characterized by the recurrent appearance of spontaneous seizures due to pathological hyperexcitability and sudden abnormal discharge ofThe amygdala is among the most vulnerable areas to kindling [1, 3]
Sayahi et al The Journal of Physiological Sciences (2022) 72:1 plays a key role in cognitive and emotional functions [5], the amygdala dysfunction in temporal lobe epilepsy (TLE) is essential for its role in the generation of seizures, and for its role in the psychological disorders that are often associated with epilepsy [3, 6]
In the present study in an effort to better understand the relationship between epilepsy and the 5-HT3 receptors in entorhinal cortex (EC), the effects of 5-HT3 receptor antagonist—ramosetron—on the severity of seizures was investigated
Summary
Epilepsy is a chronic neurological disorder, with a prevalence of about 1%, which is characterized by the recurrent appearance of spontaneous seizures due to pathological hyperexcitability and sudden abnormal discharge ofThe amygdala is among the most vulnerable areas to kindling [1, 3]. Sayahi et al The Journal of Physiological Sciences (2022) 72:1 plays a key role in cognitive and emotional functions [5], the amygdala dysfunction in TLE is essential for its role in the generation of seizures, and for its role in the psychological disorders that are often associated with epilepsy [3, 6]. Using this model, evaluating the possible involvement and anticonvulsant effects of major neurotransmitter systems in nervous system can be done. Hippocampal memory function depends on an intact EC [9]
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