Mechanisms of seizure control mediated by gamma-aminobutyric acid: role of the substantia nigra

Abstract

The substantia nigra has been identified as a critical site at which gamma-aminobutyric acid (GABA) agonist drugs act to reduce susceptibility to a number of types of experimentally induced generalized seizures. Moreover, the ability of systemically administered GABA-elevating agents to protect against maximal electroshock seizures is directly correlated with an increase in GABA specifically in the nerve-terminal compartment of substantia nigra. The significance of these findings is discussed in terms of the role of specific nigral synapses for the control of seizure propagation. Evidence from lesion studies, as well as studies with opiates and substance P analogs, further supports the hypothesis that Inhibition of nigral efferents reduces susceptibility to generalized seizures. Inhibition of nigral outflow causes a decreased sensitivity to chemoconvulsants without precluding the animal's ability to exhibit any or all of the motor components of a seizure. We therefore propose that nigral outputs are capable of facilitating seizure propagation and can function as a gating mechanism for the generalization of convulsive activity.