海馬キンドリング発作におけるセロトニン作動系の関与—セロトニン2受容体アゴニスト1—（2,5—dimethoxy−4—iodophenyl）−2—aminopropaneおよびアンタゴニストketanserinの効果

Serotonergic Mechanisms of Hippocampal Kindled Seizures in Cats : Effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and Ketanserin

　前報（脳神経44：989-993, 1992）でセロトニン（5—HT）前駆物質L−5—hydroxytryptophan，5—HT1a受容体アゴニスト8—hydroxy−2—（di-n—propylamino）tetralinの海馬キンドリング発作に対する効果を検討し，海馬発作の発現における5—HT₁a受容体の抑制的関与を報告した。今回は5—HT₂受容体の役割を明らかにする目的で，5—HT₂受容体アゴニスト1—（2.5—dimethoxy−4—iodophenyl）−2—aminopropane（DOI）および5—HT2受容体アンタゴニストketanserinの投与実験を行った。その結果，両剤ともに行動上の発作段階には効果を示さなかったものの，DOI投与により全身けいれん発作が発現するまでの潜時および後発射持続時間が有意に短縮した。他方，ketanserin投与では全身けいれん発作の発現潜時の有意な延長を認めた。前報と今回の成績から，海馬発作におけるセロトニン系の作用は受容体サブタイプによって異なり，5—HT₂受容体は発作の二次性全般化に促進的に関与している可能性が示唆された。

Based on our previous findings that a serotonin (5-HT) precursor L-5- hydroxytryptophan and a 5-HT₁a receptor agonist 8-hydroxy-2- (di-n-propylamino) tetralin can suppress seizures kindled from the feline hippocampus (HIP) , we have sug-gested that 5-HT₁a receptors play an inhibitory role in HIP seizure generation. In order to clarify the role of 5-HT₂ receptors in epilepsy, the present study examined the effects of a 5-HT₂ receptor agonist 1- (2,5-dimethoxy-4-iodophenyl) -2-amino-propane (DOI) and a 5-HT₂ receptor antagonist ketanserin on HIP-kindled seizures.

Following the completion of HIP kindling, five cats received intravenous injections of 0.9% saline, DOI (1.0mg/kg) or ketanserin (1.0mg/kg). Electri-cal stimulation at the generalized seizure trigger-ing threshold was delivered to the kindled HIP 15 min after drug administration. The anticonvulsant effects were assessed by the behavioral seizure stage, afterdischarge duration, latency to the onset of stages 4 and 6, and duration of a generalized tonic-clonic convulsion (GTC).

Although no significant change was found in the seizure stage following the administration of either drug, both DOI and ketanserin significantly alte-red the latency for seizure generalization. DOI significantly reduced the latency to the onset of stage 6 GTC as compared with saline, with a significant reduction in the afterdischarge duration. In contrast, ketanserin significantly increased the latency to the GTC onset as compared with saline. Neither the latency of the stage 4 onset nor the GTC duration was significantly affeced by these drugs.

These results, together with our previous data, indicate that the role of 5-HT in HIP seizures differs depending upon the 5-HT receptor subtypes, and suggest that 5-HT, receptors may play an excitatory role in kindled seizure generalization from the HIP.