Neurosteroidal modulation of in vitro epileptiform activity is enhanced in pilocarpine-treated epileptic rats

• THDOC application to pilocarpine-treated slices abolished ictal discharges in PC and EC in one third of experiments.
• THDOC application to pilocarpine-treated slices reduced frequency and duration of ictal discharges in remaining experiments.
• THDOC application increased occurrence of ripples and fast ripples associated to interictal events.
• THDOC application to pilocarpine-treated slices modified pattern of HFO occurrence during ictal discharges in both PC and EC.

We employed field potential recordings in brain slices obtained from pilocarpine-treated epileptic (4–5 weeks following a pilocarpine-induced status epilepticus) and age-matched, non-epileptic control (NEC) rats to establish the effects of the neurosteroid allotetrahydrodeoxycorticosterone (THDOC) on the epileptiform activity – including high frequency oscillations (HFOs; ripples: 80–200 Hz, fast ripples: 250–500 Hz) – induced by 4-aminopyridine (4AP) in piriform (PC) and entorhinal (EC) cortices. Both structures are highly susceptible to generate seizures and may also be involved in epileptogenesis. We found that THDOC application to pilocarpine-treated slices: (i) decreased interictal discharge frequency in PC while increasing it in EC; (ii) abolished ictal discharges in both areas in approx. one third of the experiments and reduced them in frequency and duration in the remaining experiments; and (iii) increased the occurrence of ripples and fast ripples associated to interictal events, and modified their pattern of occurrence during ictal discharges in both PC and EC. These effects were either weaker or absent in NEC tissue. Our results demonstrate that THDOC plays a structure-dependent modulatory role in epileptiform synchronization in the pilocarpine-treated epileptic rat brain where its actions are more pronounced than in NEC tissue. This evidence supports the application of neurosteroids as potential antiepileptic tools.