The differential effects of protein synthesis inhibition on the expression and reconsolidation of pentylenetetrazole kindled seizures

This work attempted to answer the question whether the central processes engaged in the memory formation and the epilepsy development are governed by the overlapping mechanisms. The effects of the protein synthesis inhibitor cycloheximide (CHX) were examined on the expression and reconsolidation of pentylenetetrazole (PTZ) – induced kindled seizures and for comparative purposes, on the reconsolidation of conditioned fear response (conditioned freezing). It was found that post-test intracerebroventricular administration of CHX (125 µg/5 µl) significantly attenuated the expression of a conditioned fear response examined 24 h later. Thus, inhibition of de novo brain protein synthesis interfered with the reconsolidation of a conditioned response. CHX given at the same dose repeatedly to fully kindled rats immediately after three consecutive sessions of PTZ-induced seizures (35 mg/kg ip) did not modify the strength of convulsions. On the other hand, CHX significantly attenuated the strength of convulsions when the drug was administered 1 h before the PTZ injection, which occurred every second day for three consecutive sessions. However, when CHX was omitted in a consecutive session, PTZ induced a fully developed expression of tonic-clonic convulsions, thereby indicating that CHX-induced changes in seizure intensity were transitory. Western Blot analysis confirmed that CHX potently inhibited PTZ-induced protein synthesis (c-Fos) in the rat brain, examined 60 min after CHX and PTZ administration. The present findings suggest that the mechanisms underlying kindling are resistant to modification, even under the influence of protein synthesis inhibitors, and that there are important differences between the processes of learning and kindling seizures.