Effect of microinjections of gamma-vinyl GABA or isoniazid into substantia nigra on the development of amygdala kindling in rats.

The effects of bilateral microinjections into the substantia nigra pars reticulata of gamma-vinyl GABA and isoniazid, i.e., drugs which manipulate GABA-mediated inhibition, were studied on kindling and kindled seizures induced by daily stimulation of the amygdala in rats. In comparison to saline-injected controls, both gamma-vinyl GABA (5 or 10 micrograms) and isoniazid (150 micrograms/side) retarded the rate of kindling development as measured by the increase in seizure severity. The duration of the motor seizures and the duration of afterdischarges recorded from the stimulated amygdala were less sensitive to the anticonvulsant effect of both drugs, although significant reductions were measured during kindling acquisition. In fully kindled rats, only gamma-vinyl GABA exerted significant effects on kindled seizures, whereas isoniazid was ineffective after intranigral injection, suggesting that the kindling acquisition period is more sensitive to alterations in GABA-mediated transmission than the fully kindled state. The data provide further evidence that the substantia nigra is involved in the development and expression of kindled seizures.