Substantia nigra pars reticulata lesion induces preconvulsive behavior and changes in glutamate receptor gene expression in the rat brain.

Abstract The substantia nigra pars reticulata (SNpr) has been proposed to play an important role in the control of the propagation and/or the generation of epileptic seizures. Earlier studies have shown differential effects of the lesion of the SNpr on seizure genesis that demonstrated a regional difference in the anterior and posterior parts of the SNpr in preconvulsive behavior induced by unilateral reticulata injection of dopamine (DA). This study was aimed to investigate some of the underlying mechanisms of the preconvulsive behavior elicited by unilateral SNpr DA injection by the study of changes in the gene expression of glutamate receptor subunits (GluR1, GluR2 and NMDAR1) and of changes in animal behavior following coinfusion of DA and a DA D1 antagonist SCH 23390 into the SNpr. Unilateral injection of exogenous DA into the anterior region of the SNpr induced rapid and short lasting preconvulsive behavior up to wet dog shakes stage and a significant reduction of gene expression for GluR1, GluR2 and NMDAR1 subunits in rat hippocampal subfields including CA1 through CA4 and dentate gyrus (DG) at 1 day after nigral DA injection. The effect was long lasting and persisted for at least 3 weeks. Both preconvulsive behavior and downregulation of glutamate receptor subunit genes were completely blocked by simultaneous coinfusion of DA and SCH 23390. The results suggest, for the first time, that DA D1 receptor in the SNpr may mediate the nigral-involved seizure development. Glutamate desensitization, and/or selective early neuronal damage might be responsible for the downregulation of glutamate receptor subunits by transient preconvulsive activity.