Effect of cycloheximide on the initiation and maintenance of increased seizure readiness in the rat sensorimotor cortex

Abstract

Cycloheximide does not affect the thresholds of elicitation of either direct or transcallosal responses of the sensorimotor cortex, the poststimulation elevation of brain excitability immediately after termination of the 20th series of rhythmic electrostimulations, or the diminishment of its excitability 24 h later. Cycloheximide administration does not change the latency or the duration of the frost seizure discharge but does abolish the potentiation of the duration of the seizure discharges. When tested again a day later, control rats exhibit a marked decrease of the latency of the first seizure discharge and an increase of discharge amplitude as compared to the corresponding parameters in the first series of rhythmic electrostimulations. Key Words: increased seizure readiness; cycloheximide; sensorimotor cortexRepeated rhythmic electrical stimulations (RES) of the sensofirnotor cortex of the rat brain induce trace seizure discharges (SD) of the peak-wave type which increase in amplitude and duration during subsequent RES. Increased seizure readiness develops after 1-2 h of RES, when all RES series without exception induce trace discharges of the same amplitude and duration [1]. The second RES session performed 24 h later attests to the preservation of the state of increased seizure readiness during this period. The elicitation of the first SD requires far fewer stimulations in the second RES, and all SD themselves induced in this ease are of higher amplitude than the SD recorded during the first RES session [2].Inhibitors of protein synthesis inhibit RES-induced long-term modifications of the neuronal excitability, attesting to the key role of protein synthesis in consolidating the heightened excitability of neurons. Thus, the inhibitor of protein synthesis cycloheximide (CH) obstructs SD potentiation in the amygdala and markedly delays the development of kindling [6,8]. Anisomycin-induced blockade of proResearch Institute of General Pathology and Pathological Physiology, Russian Academy of Medical Sciences, Moscow rein synthesis keeps the hippocampus from developing the late phase of long-term potentiation [5]. The present study was undertaken to explore the possible role of protein synthesis in eliciting and maintaining the state of increased seizure readiness in the sensorimotor cortex. For this purpose the effect of CH on SD parameters was studied in two identical RES sessions conducted 24 h apart. MATERIALS AND METHODSExperiments were carried out on 50 outbred male rats weighing 280-350 g. Control animals (38 rats) were injected i.p. with 0.5 ml physiological saline, while the 12 experimental rats received i.p. 0.5 ml CH (Serva, 2 mg/~) 1.5-2 h prior to the operation. Electrodes placed on the undamaged dura mater were used to stimulate a region of the sensorimotor cortex of the right hemisphere and to record the eleetrocorticogram from this region as well as from the symmetrical one in the contralateral hemisphere [1]. The experiment was begun by determining the thresholds of the direct and transcallosal ...