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.
Okada
R
R
Department of Psychiatry, School of Medicine, Juntendo University, Tokyo, Japan.
Negishi
N
N
Nagaya
H
H
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D010433:Pentylenetetrazole; D011149:Pons / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D013477:Superior Colliculi / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D010433:Pentylenetetrazole; D001640:Bicuculline