Serotonin modulates fast ripple activity in rats with spontaneous recurrent seizures

Fast ripples (FRs) are pathological high frequency oscillations that occur in patients with temporal lobe epilepsy (TLE), as well as in animal models of epilepsy in which seizures are induced with kainic acid or pilocarpine. These oscillations have been considered potential biomarkers of epileptogenesis in the hippocampus. Indeed, experimental evidence suggests an important role of serotonin in epilepsy and an increased frequency of FRs have been demonstrated in slow wave sleep, a period during which serotonin levels decrease. Accordingly, we investigated the role of serotonin in FRs modulation by evaluating the effects of citalopram, a blocker of serotonin uptake, on the occurrence of spontaneous FRs measured through intracranial bilateral EEG recording of the hippocampus of rats with spontaneous recurrent seizures. In addition, we recorded the mean number of oscillation cycles per FRs event and the average frequency (Hz) before, during and after citalopram administration in order to determine whether increases in extra-synaptic serotonin levels modulate FRs. The elevation of serotonin levels induced by citalopram (4.78 ± 1.69 nM) reduced the occurrence of spontaneous FRs (57%), the mean number of oscillation cycles per FRs event (34%) and the average frequency of FRs (33%). These findings suggest an important modulatory effect of serotonin on FRs.