Depaulis A, Vergnes M, Liu Z, Kempf E, Marescaux C
Département de Neurophysiologie et Biologie des Comportements, Centre de Neurochimie du CNRS, Strasbourg, France.
Neuroscience. 1990;39(2):339-49. doi: 10.1016/0306-4522(90)90272-6.
Activation of GABAergic transmission within the substantia nigra has been shown to suppress several forms of generalized seizures in experimental models of epilepsy. More especially, such pharmacological manipulations suppress spontaneous and chemically-induced generalized non-convulsive seizures in the rat. The aim of the present study was to examine the role of the dopaminergic and GABAergic thalamic and collicular nigral outputs in this antiepileptic effect. For this purpose, we examined the effects of output destruction on the antiepileptic effect of intranigral injections of a GABA agonist or pharmacological blockade of the neurotransmission at the nerve terminal level in rats with spontaneous absence seizures. After selective destruction of dopaminergic neurons within the substantia nigra with 6-hydroxydopamine (5 micrograms/side) or hemisection of the ascending nigral output, bilateral intranigral injection of muscimol (2 ng/side) still significantly suppressed generalized non-convulsive seizures. Bilateral lesioning of the ventromedial nucleus of the thalamus did not abolish the antiepileptic effects of intranigral muscimol (2 ng/side) and the GABA antagonist, picrotoxin, when given into this thalamic nucleus (10 ng/side) also failed to induce suppression of spike and wave discharges. The antiepileptic effects of intranigral injection of muscimol (2 ng/side) was reversed by bilateral electrolytic lesions of the superior colliculus. Blockade of the GABAergic transmission at this level with picrotoxin (40 ng/side) significantly suppressed generalized non-convulsive seizures. Finally, excitation of collicular cell bodies with low doses of kainic acid (4 and 8 ng/side) also resulted in a suppression of spike and wave discharges. These results demonstrate that the GABAergic nigrocollicular pathway is critical for the inhibitory control of the substantia nigra over generalized non-convulsive seizures. The data further suggest that antiepileptic effects observed following potentiation of GABAergic transmission in the substantia nigra result from a disinhibition of collicular cell bodies.
在癫痫实验模型中，黑质内GABA能传递的激活已被证明可抑制多种形式的全身性癫痫发作。更具体地说，这种药理学操作可抑制大鼠自发性和化学诱导的全身性非惊厥性癫痫发作。本研究的目的是研究多巴胺能和GABA能丘脑及中脑黑质传出纤维在这种抗癫痫作用中的作用。为此，我们在自发性失神发作的大鼠中，研究了传出纤维破坏对黑质内注射GABA激动剂的抗癫痫作用或神经末梢水平神经传递的药理学阻断的影响。在用6-羟基多巴胺（5微克/侧）选择性破坏黑质内的多巴胺能神经元或切断黑质上行传出纤维后，双侧黑质内注射蝇蕈醇（2纳克/侧）仍能显著抑制全身性非惊厥性癫痫发作。丘脑腹内侧核的双侧损伤并未消除黑质内注射蝇蕈醇（2纳克/侧）的抗癫痫作用，并且当将GABA拮抗剂印防己毒素注入该丘脑核（10纳克/侧）时，也未能抑制棘波和慢波放电。双侧上丘电解损伤可逆转黑质内注射蝇蕈醇（2纳克/侧）的抗癫痫作用。用印防己毒素（40纳克/侧）阻断该水平的GABA能传递可显著抑制全身性非惊厥性癫痫发作。最后，用低剂量的 kainic 酸（4和8纳克/侧）刺激中脑细胞体也可导致棘波和慢波放电的抑制。这些结果表明，GABA能黑质-中脑通路对于黑质对全身性非惊厥性癫痫发作的抑制控制至关重要。数据进一步表明，在黑质中增强GABA能传递后观察到的抗癫痫作用是由于中脑细胞体的去抑制作用。
