The role of noradrenaline in the model of stress-induced seizures

Stress is one of the most frequently self-reported precipitants for seizure induction in epilepsy patients, but how stress triggers seizures remains unknown. In the medial prefrontal cortex (mPFC), stress has been known to enhance the release of noradrenaline (NA), which excites mPFC layer 5 (L5) pyramidal cells. Thus, we investigated the possible contribution of NA in the mPFC to stress-induced epileptic seizures. Intra-mPFC infusion of picrotoxin (0.1 nmol/side) and NA (10 nmol/side) induced seizures with shorter latency than that of picrotoxin alone in C57BL/6J mice. In vitro whole-cell patch-clamp recordings from mPFC L5 pyramidal cells revealed that, in the presence of picrotoxin (30 µM), bath-application of NA (10 µM) induced rhythmic and frequent epileptiform activities (EA) consisting of prolonged depolarization with burst firings in short latency, while picrotoxin alone induced sporadic and long-latency EA. The NA-induced EA were inhibited by terazosin (5 µM), but not atipamezole (3 µM) or timolol (10 µM), indicating the involvement of α1 adrenoceptors for the EA generation. These results suggest that NA released in the mPFC might contribute to the expression of stress-induced seizures in epilepsy patients.