Objectives: There is a strong relationship between absence seizures and sleep-wake states observed in genetic generalized epilepsy syndromes. Neurotensin (NT) has been shown to play an important role in maintaining the activity of orexin-producing neurons in the lateral hypothalamus as well as physiological regulation of sleep/wake states. NT and orexin receptors are both strongly expressed in layer 6b cortical neurons in the rodent brain and some of these neurons have extensive intracortical and thalamic projections. In this study we tested the hypothesis that NT may have a modulatory role in the occurrence of absence seizures. We studied the effect of intracerebroventricularly (ICV) administered Neurotensin-1 (NT-1) receptor agonist NT on spike-and-wave discharges (SWDs) in electroencephalography (EEG) of Genetic Absence Epilepsy Rat from Strasbourg (GAERS), the most commonly used rat model of genetic absence epilepsy.

Materials-Methods: ICV cannula and EEG electrodes were stereotaxically implanted in adult male GAERS under ketamine/xylazine anesthesia. After one-week recovery, baseline EEG was recorded and then, NT at three different concentrations (0.5, 1 and 1.5 nmol/10μl) and 10μl of saline to the control group were administered ICV and EEG was recorded for 3 hours. The total duration, number and average duration of SWDs were analyzed.

Results: The cumulative SWD duration and the mean duration of individual SWD in the 1. 5nmol/10μl NT administered GAERS was significantly suppressed especially around the 120 minute of post injection period compared to control (p<0.05). However, no significant change was observed in the SWD number. There was no significant effect on SWDs in the groups treated with lower concentrations of NT.

Conclusion: Our study revealed a suppressive effect of NT on SWDs in GAERS for the first time suggesting that neuropeptidergic signaling may have a modulating effect on absence seizures. The challenge is to determine whether this effect is mediated on cortical or subcortical level.

Keywords: Neuropeptide, Absence epilepsy, Neurotensin, GAERS