Probenecid誘発けいれんと髄液中環状ヌクレオチド—Kindling preparationを用いた実験的研究

PROBENECID-INDUCED CONVULSION AND CEREBROSPINAL CYCLIC NUCLEOTIDES IN THE KINDLING CAT PREPARATIONS

緒言

　脳内モノアミンがてんかん発作の発現やけいれん準備状態と密接な関連をもち，実験てんかんモデル"kindli—ng preparation"による研究でも脳内カテコラミンの抑制的な役割りが報告されている^3,8,11,13）。最近はさらに脳内モノアミン濃度の変化だけでなく，それらの受容体の感受性が注目されており^14），受容体の感受性や細胞内情報伝達にかかわる環状ヌクレオチドとてんかんとの関連をとりあげた研究があいついでみられる。Dibutyryl—cAMPの大槽内投与でけいれんが誘発されたというGessaの報告^5）以来，脳あるいは脳脊髄液（cerebrospinalfluid,CSF）中の3'，5'—cyclic adenosine monophosphate（cAMP），3'，5'—cyclic guanosine monophosphate （cGMP）の高値とてんかん発作の発現，あるいはけいれん準備状態とを関連づける報告が多い^2,7,15,18）。

　しかしごく最近秋山^1）は，けいれん準備状態やけいれん発作と対応したCSF中cAMP，cGMP濃度の変化をkindling cat preparationを用いて検討し，けいれん準備状態が形成されるとCSF中環状ヌクレオチド濃度は有意に減少することを見出している。そしてこの環状ヌクレオチド濃度の減少がkindling preparationですでに報告されている脳内カテコラミン濃度の減少^3,11）や，てんかん患者のCSFで報告されているhomova—nillic acid （HVA）濃度の減少と関連づけた考察を試みた^1）。

A number of recent papers have related an in-creased concentration of brain cyclic nucleotide to seizure susceptibility in various experimental models of epilepsy. However, Akiyama has recently found a significant decrease in CSF cAMP and cGMP in amygdaloid kindled cats, and stressed an inhibitory role of cyclic nucleotides on seizure susceptibility. During a series of such experiment, we found that probenecid (150mg/kg) induced generalized con-vulsions in the kindled cats frequently. Behavioral, electrographic observation and measurement of CSF cyclic nucleotides were made in this study. Following results were obtained; (1) Probenecid (150mg/kg, i. p.) induced generalized convulsions more frequently in the kindled group (3 of 4 cats) than the control group (2 of 8 cats). Tonic, tonic-clonic generalized seizure appeared 30-60 minutes after the injection, and was easily triggered by external stimuli (i. e. loud sound, touch). (2) Dose dependent increase in interictal spike discharges was observed only in the kindled cats. (3) CSF cGMP concentration was significantly higher in the cats without induced-convulsion than the cats with convulsions, while no difference was found in CSF cAMP concentration (at 60 minutes after the probenecid injection). (4) Transfusion of cis-ternal CSF of the convulsed cats into the control cats induced no behavioral or electrographic change.

These findings indicated a lower threshold for probenecid-induced convulsions in the kindled cats than the control cats. No relation was found be-tween CSF cAMP and probenecid-induced con-vulsions.