EPISODIC BARREL ROTATIONS INDUCED BY INTRASTRIATAL INJECTION OF QUINOLINIC ACID IN RATS - INHIBITION BY ANTICONVULSANTS
EPISODIC BARREL ROTATIONS INDUCED BY INTRASTRIATAL INJECTION OF QUINOLINIC ACID IN RATS - INHIBITION BY ANTICONVULSANTS
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DOI：
10.1016/0091-3057(88)90327-9
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发表时间：
1988-09-01
影响因子：
3.6
通讯作者：
WAUQUIER, A
中科院分区：
文献类型：
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作者：
MARRANNES, R;WAUQUIER, A
在大鼠一侧纹状体内注射喹啉酸(2，3-吡啶二羧酸盐；奎宁)，会产生间歇性的桶旋转和紧张性-阵挛前爪运动，持续几个小时。我们调查了在这种现象已经完全发展的情况下，使用抗惊厥药物后的腹膜腔内治疗是否可以消除这种现象，以及在癫痫模型中，它们的效力比率是否相似。所有受试的8种抗癫痫药物，即卡马西平、氯硝西潘、安定、二苯基海因、乙硫胺、氟桂利嗪、苯巴比妥和丙戊酸钠均以剂量依赖的方式减少这种行为。其他六种具有抗惊厥作用的药物也有效：DL-2-氨基-7-膦庚酸、地昔帕明、依托咪酯、氯胺酮、甲丙氨酸酯和沙贝鲁唑。在最大美曲唑惊厥试验中，将桶旋转次数减半的ED50值与发表的抑制紧张性后掌伸展的ED50值有很好的相关性(rS=.95，p<；0.001)，与在大鼠点燃模型中将前爪阵挛的持续时间减半的ED50值(rS=.93，p<；0.001)有很好的相关性。这种喹啉酸试验可以直观地显示抗惊厥药物的作用开始，每种动物都作为自己的对照。本实验还观察了多巴胺拮抗剂氟哌啶醇和匹莫齐特、乙酰胆碱酯酶抑制剂毒扁豆碱以及抗胆碱药物阿托品和地塞米特对影响亨廷顿S病症状的药物是否也敏感。实验结果表明，纹状体内注射奎宁后仅3-6小时，桶旋转和阵挛前爪运动对抗惊厥药物有反应，但对对症治疗亨廷顿S病的药物不敏感。
Unilateral intrastriatal injection of quinolinic acid (2,3 pyridine dicarboxylate; QUIN) in the rat produces episodic barrel rotations and tonic-clonic forepaw movements, lasting for several hours. We investigated whether intraperitoneal posttreatment with anticonvulsants could abolish this phenomenon when it is already fully developed, and whether their potency ratio was similar in models of epilepsy. All 8 tested antiepileptics, namely carbamazepine, clonazepam, diazepam, diphenylhydantoin, ethosuximide, flunarizine, phenobarbital and sodium valproate decreased this behavior in a dose-dependent way. Six other drugs with anticonvulsant properties were also effective: DL-2-amino-7-phosphonoheptanoic acid, desipramine, etomidate, ketamine, meprobamate and sabeluzole. The ED50-values for halving the frequency of the episodes of barrel rotation correlated well with published ED50-values for inhibition of tonic hindpaw extension in the maximal metrazol seizure test (rs = .95, p < 0.001) and with the ED50-values for halving the duration of the forepaw clonus in the rat-kindling model (rs = .93, p < 0.001). This quinolinic acid test allows visualization of the onset of action of anticonvulsants, with each animal as its own control. In order to assess whether this test is also sensitive to drugs influencing the symptoms of Huntington''s disease, the effect of the dopamine antagonists haloperidol and pimozide, the acetylcholinesterase inhibitor physostigmine and the anticholinergics atropine and dexetimide were investigated as well. The experiments suggested that the barrel rotations and clonic forepaw movements, only 3-6 hours after intrastriatal injection of QUIN respond to anticonvulsants, but are not specifically sensitive to drugs used in the symptomatic treatment of Huntington''s disease.