FG7142 causes opposite changes in [3H]GABA release from nigrocollicular regions.

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.