Modulation of electrically evoked hippocampal epileptiform activity by exogenous orexins in the rat CA1 field

In vivo electrophysiological experiments were conducted to evaluate the effects of intraventricular and cortical administration of orexins on electrically evoked epileptiform discharges (EEDs) in the hippocampal CA1 field. Bipolar electrodes were stereotaxically implanted into the CA1 region of anesthetized rats, and epileptiform activity was induced by high‑frequency electrical stimulation (HFES). Orexin‑A and orexin‑B (10 μg/10 μl) were administered into the lateral ventricle or applied to the frontal cortex. Intracerebroventricular administration of orexin‑A significantly reduced the duration of EEDs within 20 minutes and abolished the progressive, HFES‑related prolongation of epileptiform discharges observed in control animals. In contrast, cortical administration of orexin‑A selectively reduced the incidence of high‑amplitude (7-10 mV) population spikes during EEDs without affecting the duration of epileptiform activity. Neither cortical nor intraventricular administration of orexin‑B produced significant changes in evoked epileptiform activity in the CA1 field, suggesting a possible involvement of OX1 receptor signaling in mediating the effects of orexin‑A. The differential effects observed after cortical versus intraventricular administration of orexin‑A appear to reflect site‑specific mechanisms of action. The effects of intraventricular administration of orexin‑A were predominantly induced via direct activation of hippocampal orexinergic receptors, whereas cortical application of orexin‑A induced its effects via modulation of cortico‑hippocampal mechanisms.