Effects of Cycloheximide on Experimental Epilepsy Induced by Daily Amygdaloid Stimulation in Rabbits

Ogata, Nobukuni

doi:10.1111/j.1528-1157.1977.tb05592.x

Cited by 17 publications

(6 citation statements)

References 19 publications

(13 reference statements)

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“…However, there are likely to be other proteins that are also involved in this response. Also, interestingly, the relatively early inhibitory effect (1–2 h) of cycloheximide alone against audiogenic seizure in GEP rats was in agreement with the similar onset time of action in other animal models of epileptogenesis (Ogata 1977; Williams and Jope 1994).…”

Section: Discussionsupporting

confidence: 83%

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Elevated levels of group‐III metabotropic glutamate receptors in the inferior colliculus of genetically epilepsy‐prone rats following intracollicular administration of l‐serine‐O‐phosphate

Yip

Meldrum

Rattray

2001

Journal of Neurochemistry

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The selective group-III metabotropic glutamate receptor agonist, L-serine-O-phosphate (L-SOP), when injected bilaterally into the inferior colliculus of the sound sensitive genetically epilepsy-prone (GEP) rats produces a short proconvulsant excitation followed by a long phase of protection against sound-induced seizures lasting for 2±4 days. We have studied this prolonged suppression of audiogenic seizures using pharmacological and molecular biological approaches including semiquantitative RT-PCR and western blotting. The intracerebroventricular injection of the protein synthesis inhibitor cycloheximide (120 mg) 30 min beforehand signi®cantly reduces the proconvulsant seizure activity and the prolonged anticonvulsant effect of intracollicular L-SOP (500 nmol/side). The sensitive semiquantitative RT-PCR revealed a signi®cant up-regulation in mGlu 4 and mGlu 7 mRNA levels in the inferior colliculus at 2 days (maximum suppression of audiogenic seizures) after intracollicular L-SOP injection compared with the non-injected, 2-day post-vehicle treated and 7-day (return to expressing audiogenic seizures) post-drug or vehicletreated groups. No signi®cant changes were observed in mGlu 6 or mGlu 8 mRNA expression levels in drug-treated compared with control groups. Examination of mGlu 4a and mGlu 7a protein levels using western blotting showed a signi®cant increase in mGlu 7a but no signi®cant change in mGlu 4a protein levels 2 days after L-SOP treatment compared with the control groups (non-injected and 2-day vehicleinjected group). These results suggest that up-regulation of mGlu 7 receptors is involved in the prolonged anticonvulsant effect of L-SOP against sound-induced seizures in GEP rats. The potential use of mGlu 7 agonists as novel anti-epileptic agents merits investigation.

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Section: Discussionsupporting

confidence: 83%

“…This time‐course suggests that de novo protein synthesis may be involved. Previous studies in epilepsy have shown the protein synthesis inhibitor, cycloheximide to attenuate seizures in rats induced by lithium plus pilocarpine (Williams and Jope 1994), and to suppress focal after‐discharge in amygdaloid‐stimulated rabbits (Ogata 1977).…”

mentioning

confidence: 99%

Elevated levels of group‐III metabotropic glutamate receptors in the inferior colliculus of genetically epilepsy‐prone rats following intracollicular administration of l‐serine‐O‐phosphate

Yip

Meldrum

Rattray

2001

Journal of Neurochemistry

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“…These data are reminiscent of the same effect of protein synthesis inhibitors on posttetanic potentiation in the hippocampus, the early stage of which is resistant to the action of CH and anisomycin, whereas the longterm stage is abolished by them [7,11]. Abolished potentiation of SD duration as well as delayed development of the generalized seizure syndrome have been described previously in studies of classical amygdalar kindling [8,10].…”

Section: Resultsmentioning

confidence: 55%

“…As has been shown in acute experiments on the hippocampus, rhythmic stimulation of the afferent tract markedly weakens GABAergic inhibition [12,13]. The decreased inhibition of neurons observed in kindling is probably due to the selective death of interneurons [10].…”

Section: Resultsmentioning

confidence: 96%

“…It is assumed that the development of seizure readiness in kindling is due to the synthesis of new proteins [8,10]. Data on the effect of protein synthesis inhibitors on long-term potentiation of the exciting postsynaptic potential in the dentate gyms attest that the synthesis of proteins required for the maintenance of heightened neuronal excitability terminates 15 min after the end of tetanization.…”

Section: Resultsmentioning

confidence: 99%

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

1995

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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 ...

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Pharmacological Prophylaxis in the Kindling Model of Epilepsy

Wada¹

1977

Archives of Neurology

126

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Review of antiepileptic drug assessment to date by means of the kindling model of epilepsy suggests that it fills a gap that is evident in standard screening methods such as maximum electroshock or pentylenetetrazol screening tests. However, in order to obtain a comprehensive profile of antiepileptic drugs regarding prophylaxis of developing seizures and treatment of well-established seizures through the kindling preparation, it is desirable to have the following: (1) standardization of kindling techniques, (2) examination of drug effects on developing as opposed to developed seizures, (3) use of a variety of animal species, involving different functional brain sites, and (4) monitoring of plasma levels of the drug administered. It is envisaged that judicious use of the kindling preparation might also enable us to gain some insight into the mechanisms by which drugs produce their prophylactic or therapeutic effect.

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Effects of Cycloheximide on Experimental Epilepsy Induced by Daily Amygdaloid Stimulation in Rabbits

Cited by 17 publications

References 19 publications

Elevated levels of group‐III metabotropic glutamate receptors in the inferior colliculus of genetically epilepsy‐prone rats following intracollicular administration of l‐serine‐O‐phosphate

Elevated levels of group‐III metabotropic glutamate receptors in the inferior colliculus of genetically epilepsy‐prone rats following intracollicular administration of l‐serine‐O‐phosphate

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

Pharmacological Prophylaxis in the Kindling Model of Epilepsy

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