The role of the nigrotegmental GABAergic pathway in the propagation of pentylenetetrazol-induced seizures.

Recent evidence suggests that the substantia nigra (SN) may be involved in the modification of various experimental epilepsy models. We determined the role of gamma-aminobutyric acid (GABA)ergic activity of the SN and the target sites of SN efferents, the pedunculopontine nucleus (PPN) and superior colliculus (SC), in pentylenetetrazol-induced seizures in rats. Bilateral administration of a GABA agonist (muscimol) into the SN significantly reduced seizure severity; its administration into the PPN significantly augmented seizure severity; administration into the SC did not alter the seizure severity. On the other hand, infusion of a GABA antagonist (bicuculline) into the PPN revealed a protective effect against seizures. Our findings indicate that the nigral GABAergic projections to the PPN play an important role in seizure propagation. Thus, PPN neurons may be a possible target site of nigral output modulating seizure propagation.