Substantia Nigra Dopamine Infusion: Behavioral and Biochemical Correlates
In this study, exogenous dopamine (DA) was unilaterally infused into the anterior and posterior portions of the SN pars reticulata. This was followed by evaluation of animal behavior and changes in the expression of Fos oncoprotein (a marker for neuronal activity) and glutamate receptor subunit genes. The study was designed to investigate the effects of unilateral SN pars reticulata injection of DA on seizure generation and to elucidate the potential mechanisms involved. Unilateral infusion of exogenous DA [1.5 or 2 [mu]mole in 2 [mu]l of phosphate buffered saline (PBS)] into the anterior region of the SN pars reticulata induced preconvulsive behavior up to the "wet dog shakes" stage approximately 3 hours following injection and lasted 6-10 hours. This seizure induction was observed in ninety percent of rats receiving the treatment, while the same injection into the posterior portion of the SN pars reticulata did not produce seizure behavior in most rats. Rats exhibiting preconvulsive behavior elicited by unilateral DA infusion into anterior SN pars reticulata showed transient Fos expression in limbic structures, especially in hippocampus. Fos expression started approximately 3 hours after DA injection, peaked at 9-12 hours and gradually decreased by 24 hours. A significant reduction of gene expression for GluRl, GluR2 and NMDAR1 subunits was found in rat hippocampal subfields including CA1 through CA4 and dentate gyrus (DG) at 1 day and 3 weeks after nigral DA injection. The preconvulsive behavior and the downregulation in GluRl, GluR2 and NMDAR1 mRNA was completely blocked by coinfusion of DA and DA D1 antagonist SCH 23390. These findings support the following: (1) The anterior and posterior portions of the SN pars reticulata exert differential influence on seizure development: DA injection into anterior SN pars reticulata may facilitate seizure genesis; (2) The mechanism for the seizure development may possibly be DA D1 receptor mediated through striato-nigro-thalamocortical pathway. The mechanism for the downregulation of glutamate receptor subunit genes is not yet known, but glutamate desensitization, or selective early neuronal damage might be involved. (Abstract shortened by UMI.)
Advisor:Juorio, Augusto V.
School:University of Saskatchewan
School Location:Canada - Saskatchewan
Source Type:Master's Thesis
Keywords:no keywords supplied
Date of Publication:01/01/1998