Hippocampal and Septal 5-HT1A Receptor Expression in Two Rat Models of Temporal Lobe Epilepsy

and clinical data suggest an impact of serotonergic signaling on seizure susceptibility and epilepsy-associated psychiatric comorbidities. Previous mPET studies revealed increased binding of the 5HT1A receptor ligand [18F]MPPF in two rat models with spontaneous recurrent seizures. These findings raised the question whether these alterations are due to altered 5-HT1A receptor expression or a modification of extracellular serotonin concentrations. 5-HT1A receptor expression rates were quantitatively analyzed in rat brain tissue from an electrical and a chemical post-status epilepticus model. Based on the mPET findings, stereological analysis was focused on hippocampal subregions and the septum. Evaluation of 5-HT1A receptor expression in the electrical post-status epilepticus model revealed a decreased optical density in hippocampal CA3 region. In all other brain regions of interest, the analysis demonstrated comparable 5-HT1A receptor expression rates among all experimental groups in the brain regions evaluated. Moreover, 5-HT1A total receptor volume did not differ between groups. A model-specific correlation was demonstrated between 5-HT1A receptor expression and selected seizure and behavioral parameters. In conclusion, analysis in post-status epilepticus models in rats argued against widespread and pronounced alterations in 5-HT1A receptor expression. In view of previous mPET findings, the present data indicate that alterations in in-vivo receptor binding are due to a reduction in extracellular serotonin concentrations rather than changes in receptor density. Correlation analysis points to a possible link between 5-HT1A receptor expression and ictogenesis, seizure termination and behavioral patterns. However, as these findings proved to be model specific, the relevance needs to be further assessed in future studies focusing on other models and species. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Clinical data support the impact of serotonergic signaling on seizure susceptibility and epilepsy-associated psychiatric comorbidities. However, the study on rat models did not find widespread or pronounced alterations in 5-HT1A receptor expression in the brain, suggesting that changes in in-vivo receptor binding may be attributed to a reduction in extracellular serotonin concentrations. Correlation analysis indicates a possible link between 5-HT1A receptor expression and seizure-related parameters, warranting further investigation in other models and species.