Peris J, Scott J D
Department of Pharmacodynamics, University of Florida, Gainesville 32610.
Pharmacol Biochem Behav. 1993 Feb;44(2):333-8. doi: 10.1016/0091-3057(93)90470-e.
The activity of GABAergic neurons projecting from the striatum to the substantia nigra (SN) and from the SN to the superior colliculus (SC) may be involved in regulating seizure sensitivity such that striatonigral transmission is decreased and nigrocollicular transmission is increased in proconvulsant states. To test whether these changes occur in FG7142-treated rats, GABA transmission was assessed by measuring [3H]GABA release from superfused slices of the SN and SC and measuring [35S]TBPS binding to GABAA receptors throughout the brain. Nine daily injections of FG7142 (30 mg/kg IP) greatly increased myoclonic seizures in about one half of the animals. These animals exhibited a decrease in stimulated [3H]GABA release from the SN and an increase in both basal and stimulated release from the SC. Animals that were less sensitive to FG7142 treatment also had increased collicular release but not decreased nigral release. [35S]TBPS binding was unchanged by FG7142 treatment. Thus, decreased nigral GABA release may contribute to decreased striatonigral transmission after seizure occurrence whereas increased collicular GABA release may contribute to increased nigrocollicular transmission preceding multiple-seizure occurrence.
从纹状体投射到黑质（SN）以及从黑质投射到上丘（SC）的γ-氨基丁酸能神经元的活动，可能参与调节癫痫发作敏感性，从而在惊厥前状态下，纹状体黑质的传递减少，而黑质上丘的传递增加。为了测试这些变化是否发生在经FG7142处理的大鼠中，通过测量来自SN和SC的灌流切片中[3H]GABA的释放以及测量全脑[35S]TBPS与GABAA受体的结合来评估GABA传递。每天注射9次FG7142（30mg/kg，腹腔注射），约一半的动物出现肌阵挛性癫痫发作大幅增加。这些动物表现出SN中刺激后[3H]GABA释放减少，而SC中基础释放和刺激后释放均增加。对FG7142治疗不太敏感的动物，其丘脑中的释放也增加，但黑质中的释放未减少。FG7142处理后，[35S]TBPS结合没有变化。因此，黑质中GABA释放减少可能导致癫痫发作后纹状体黑质传递减少，而丘脑中GABA释放增加可能导致多次癫痫发作前黑质上丘传递增加。
