Zhang H, Rosenberg H C, Tietz E I
Department of Pharmacology, Medical College of Ohio, Toledo 43699.
Brain Res. 1989 May 29;488(1-2):73-9. doi: 10.1016/0006-8993(89)90694-x.
The substantia nigra pars reticulata (SNpr), a brain area rich in GABA and benzodiazepine receptors, is thought to be involved in the regulation of seizure activity. It has been shown to be a site of anticonvulsant action of substances that affect GABA transmission. The anti-pentylenetetrazol (PTZ) activities of intranigral of muscimol, a GABAA receptor agonist; two benzodiazepines, midazolam and flurazepam; and GABA were examined. Microinjection of a wide dose range of both GABA and muscimol into the SNpr failed to show anti-PTZ seizure activity. Intranigral injections of midazolam and flurazepam showed clear, dose-dependent anti-PTZ effects. Ro15-1788, a benzodiazepine receptor antagonist, reversed the anticonvulsant effects of midazolam when both were infused intranigrally. Intranigral infusion of muscimol or flurazepam protected rats from bicuculline-induced tonic seizures. The results suggest that the anti-PTZ effects of benzodiazepines in SNpr might not be mediated through GABAA receptors. Another possibility is that nigral neurons bearing GABAA receptors functionally linked to benzodiazepine sites may not be representative of the whole population of nigral neurons inhibited by GABA agonists. This could result in different patterns of inhibition of nigral efferent activity by GABAA agonists and benzodiazepines.
黑质网状部（SNpr）是一个富含γ-氨基丁酸（GABA）和苯二氮䓬受体的脑区，被认为参与癫痫活动的调节。它已被证明是影响GABA传递的物质产生抗惊厥作用的部位。研究了GABAA受体激动剂蝇蕈醇、两种苯二氮䓬类药物咪达唑仑和氟西泮以及GABA向黑质网状部内注射时的抗戊四氮（PTZ）活性。向黑质网状部内注射宽剂量范围的GABA和蝇蕈醇均未显示出抗PTZ癫痫活性。向黑质网状部内注射咪达唑仑和氟西泮显示出明显的、剂量依赖性的抗PTZ作用。苯二氮䓬受体拮抗剂Ro15 - 1788在二者均向黑质网状部内注入时可逆转咪达唑仑的抗惊厥作用。向黑质网状部内注入蝇蕈醇或氟西泮可保护大鼠免受荷包牡丹碱诱导的强直性惊厥。结果表明，苯二氮䓬类药物在黑质网状部的抗PTZ作用可能不是通过GABAA受体介导的。另一种可能性是，带有与苯二氮䓬位点功能相连的GABAA受体的黑质神经元可能不代表受GABA激动剂抑制的整个黑质神经元群体。这可能导致GABAA激动剂和苯二氮䓬类药物对黑质传出活动的抑制模式不同。
