Evaluation of the hippocampal immunoreactivity of the serotonin 5-HT1A, 5-HT2 and 5-HT7 receptors in a pilocarpine temporal lobe epilepsy rat model with fast ripples.

Abstract

Fast ripples (FRs) are found in the hippocampus of epileptic brains, and this fast electrical activity has been described as a biomarker of the epileptogenic process itself. Results from our laboratory, such as the observation of decreased seizure rates and FR incidence at a specific citalopram dose, have suggested that serotonin (5-HT) may play a key role in the FR generation process. Therefore, to gather more details about the state of the serotoninergic system in the hippocampus under an epileptogenic process, we studied the immunoreactivity of three 5-HT receptors (5-HT1A, 5-HT2 and 5-HT7) as well as the extracellular levels of 5-HT in the hippocampal tissue of epileptic rats with FR. Wistar rats (210-300 g) were injected with a single dose of pilocarpine hydrochloride (2.4 mg/2 µl) in the right lateral ventricle and video-monitored 24 h/d to detect spontaneous and recurrent seizures; microelectrodes were implanted in the dentate gyrus (DG) and CA3 and CA1 regions of these rats ipsilateral to the pilocarpine injection site 1 day after the first spontaneous seizure was observed, and only rats who suffered FR events were used in this work. Thirty-three days after the first spontaneous seizure, an immunostaining procedure and high performance liquid chromatography were performed to measure the 5-HT levels. A general depletion of the 5-HT and 5-HIIA levels in hippocampal tissue from epileptic animals compared with those in controls was observed; in addition, a general decrease in immunoreactivity for the three receptors was found, especially in the DG, which may support the establishment of an excitatory/inhibitory imbalance in the trisynaptic circuit that underlies the FR generation process.