Hippocampal and Septal 5-HT_1A Receptor Expression in Two Rat Models of Temporal Lobe Epilepsy

Experimental and clinical data suggest an impact of serotonergic signaling on seizure susceptibility and epilepsy-associated psychiatric comorbidities. Previous µPET studies revealed increased binding of the 5-HT_1A 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-HT_1A receptor expression or a modification of extracellular serotonin concentrations. 5-HT_1A receptor expression rates were quantitatively analyzed in rat brain tissue from an electrical and a chemical post-status epilepticus model. Based on the µPET findings, stereological analysis was focused on hippocampal subregions and the septum. Evaluation of 5-HT_1A 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-HT_1A receptor expression rates among all experimental groups in the brain regions evaluated. Moreover, 5-HT_1A total receptor volume did not differ between groups. A model-specific correlation was demonstrated between 5-HT_1A 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-HT_1A receptor expression. In view of previous µPET 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-HT_1A 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.