ACUTE ANTIEPILEPTIC EFFECTS OF DELTA9-TETRAHYDROCANNABINOL IN RATS WITH KINDLED SEIZURES
ACUTE ANTIEPILEPTIC EFFECTS OF DELTA9-TETRAHYDROCANNABINOL IN RATS WITH KINDLED SEIZURES
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DOI：
10.1016/0014-4886(73)90088-5
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发表时间：
1973-01-01
影响因子：
5.3
通讯作者：
WADA, JA
中科院分区：
文献类型：
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作者：
CORCORAN, ME;MCCAUGHRAN, JA;WADA, JA
我们研究了腹腔注射Δ9-四氢大麻酚（THC）对自由活动大鼠杏仁核电刺激诱发的临床和电图癫痫发作活动的急性抗癫痫作用。对大鼠进行点燃程序，即，刺激最初仅诱发局部后放电活动，但在重复给药后最终诱发传播性后放电和双侧阵挛性惊厥。在癫痫发作发展的另一个时期之后，其中建立了诱发癫痫发作的稳定性，开始药物试验。通过对每只大鼠进行多次注射检查剂量-反应关系，但每次注射之间间隔7天或更长时间，以防止耐受性或累积效应。在所有受试大鼠中，1 mg/kg或5 mg/kg Δ9-THC足以减少或阻断点燃杏仁核癫痫发作的临床表现和通常的电图表现。这些影响仅在给药当天可测量，而在随后的治疗中不可测量。在5 mg/kg剂量下出现明显的毒性行为反应，但在1 mg/kg剂量下未出现。还获得了Δ8-THC注射的初步结果。我们得出结论，Δ9-THC可以对大鼠杏仁核点燃癫痫发作发挥急性抗癫痫作用，并且这些作用可以在不一定产生总体行为毒性的剂量下发生。
We examined the acute antiepileptic effects of intraperitoneal injections of Δ9-tetrahydrocannabinol (THC) on clinical and electrographic seizure activity evoked by electrical stimulation of the amygdala in freely moving rats. The rats were subjected to a kindling procedure, viz., stimulation which initially evoked only localized afterdischarge activity but which eventually came to induce propagated afterdischarge and bilateral clonic convulsions following repeated administration. After a further period of seizure development wherein the stability of the evoked seizures was established, drug trials were initiated. Dose-response relations were examined by using multiple injections in each rat, but 7 or more days intervened between each injection to prevent tolerance or cumulative effects. Either 1 mg/kg or 5 mg/kg of Δ9-THC was sufficient to reduce or block the clinical and usually the electrographic manifestations of kindled amygdaloid seizures in all rats tested. These effects were measurable only on the day of drug administration and not in subsequent sessions. Toxic behavioral reactions were evident at the 5 mg/kg but not the 1 mg/kg dose. Preliminary results with injections of Δ8-THC were also obtained. We conclude that Δ9-THC can exert acute antiepileptic effects against kindled amygdaloid seizures in rats, and that these effects can occur at doses that need not necessarily produce gross behavioral toxicity.