Central administration of p234, kisspeptin antagonist, but not kisspeptin-10, reduces the power of epileptiform activity and slow EEG waves in male rats.

Introduction: We aimed to investigate the effects of central kisspeptin-10 and p234 administration on basal brain activity and epilepsy-like conditions induced by 4-aminopyridine (4-AP), as well as their roles in the electrocorticogram (ECoG) power spectrum and EEG waves.

Methods: Thirty-five male Wistar rats were divided into five groups: sham,4-AP (2.5 mg/kg i.p.), kisspeptin-10 post-treatment (200 pmoli.c.v.), p234 post-treatment (1 nmol i.c.v.), and p234 pre-treatment (1 nmol i.c.v.). We performed 70 minutes of recordings (10 min baseline) for all groups under ketamine/xylazine (90/10 mg/kg) anesthesia. In the post-treatment groups, kisspeptin-10 or p234 injections were administered 20 minutes after epilepsy induction. In the pre-treatment group, p234 was injected after baseline recordings. Following a 20-minute pre-treatment period, 4-AP was administered.

Results: 4-AP alone induced epileptiform activity in all animals, reaching apeak after 30 minutes. Neither kisspeptin-10 nor p234 post-treatment affected 4-AP-induced epileptiform activity (p > 0.05). However, p234 pre-treatment reduced epileptiform activity (p < 0.05). Additionally, kisspeptin-10 did not alter the spectral analysis of the EEG bands or the power of the ECoG (p > 0.05). In contrast, p234 reduced the power of the ECoG and the slow bands (delta and theta) (p < 0.05).

Conclusion: We conclude that p234 pre-treatment has an inhibitory effect on neuronal excitability and epileptiform activity in the neocortex.