A single episode of juvenile status epilepticus reduces the threshold to adult seizures in a stimulus-specific way

We have previously reported that an episode of pentylenetetrazole (PTZ)-induced status epilepticus (SE) in immature rats induces a long-term increase in cholinergic excitation assessed in the adult brain in vitro. In this in vivo work, we tested the responsiveness of adult SE-conditioned rats to pilocarpine and PTZ, two convulsants with different mechanisms of action. Postnatal day (P) 20 Sprague-Dawley juvenile rats were conditioned by an episode of PTZ-induced SE (i.e. a stage 5 seizure of ≥20 min, SE-rats). These and their untreated littermates serving as controls (seizure-naïve, SN) were challenged between P60 and P70 with subconvulsive doses of pilocarpine or PTZ, until the manifestation of a stage 5 seizure; results were also analyzed according to gender. Pilocarpine (250 mg/kg) provoked convulsive behavior in 67% of SE-rats vs 13% of SN-rats (p = 0.001); of those, 38% of SE-rats vs 4% of SN-rats reached stage 5 (p = 0.008); no gender differences were detected. PTZ provoked up to stage 4 seizures at 20 and 30 mg/kg and stage 5 seizures at 50 mg/kg in both groups without difference. Nevertheless, stage 5 seizures lasted significantly longer in SE-rats vs SN-rats (p = 0.007) and some gender differences were detected. These results show that a juvenile PTZ-induced SE increases the long-term sensitivity to a muscarinic convulsant but not to a non-cholinergic agent, suggesting a stimulus-specific decrease of the adult seizure threshold. They thus raise the possibility that adult subjects with an immature SE history may be particularly sensitive threshold-wise to stimuli that activate cholinergic mechanisms.