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

The substantia nigra pars reticulata (SNpr) has been proposed to play an im portant role in the control of the propagation and/or the generation of epi leptic seizures. Earlier studies have shown differential effects of the les ion of the SNpr on seizure genesis that demonstrated a regional difference in the anterior and posterior pal ts 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 preconvulsiv e behavior elicited by unilateral SNpr DA injection by the study of changes in the gene expression of glutamate receptor subunits (GluR1, GluR2 and NM DAR1) and of changes in animal behavior following coinfusion of DA and a DA D1 antagonist SCH 23390 into the SNpr. Unilateral injection of exogenous D A into the anterior region of the SNpr induced rapid and short lasting prec onvulsive behavior up to wet dog shakes stage and a significant reduction o f gene expression for GluR1, GluR2 and NMDAR1 subunits in rot hippocampal s ubfields including CA1 through CA4 and dentate gyrus (DG) at 1 day after ni gral DA injection. The effect was long lasting and persisted for at least 3 weeks. Both preconvulsive behavior and downregulation of glutamate recepto r subunit genes were completely blocked by simultaneous coinfusion of DA an d SCH 23390. The results suggest, for the first time, that DA D1 receptor i n the SNpr may mediate the nigral-involved seizure development. Glutamate d esensitization. and/or selective early neuronal damage might be responsible for the downregulation of glutamate receptor subunits by transient preconv ulsive activity. (C) 2000 Elsevier Science B.V. All rights reserved.