Lesion of Subthalamic Nucleus in Parkinsonian Rats : Effects of Dopamine D 1 and D 2 Receptor Agonists on the Neuronal Activities of the Substantia Nigra Pars Reticulata

Abstract

It was hypothesized that dopamine agonist administrationand subthalamic nucleus (STN) lesion in the rat might havea synergistic effect on the neuronal activities ofsubstantia nigra pars reticulata (SNpr) as observed inpatients with Parkinson's disease. The effects of SKF38393(a D(1) receptor agonist) and Quinpirole (a D(2) receptoragonist) were compared in parkinsonian rat models with 6-hydroxydopamine (6-OHDA) after STN lesion.SKF38393 andQuinpirole were consecutively injected intrastriatally.SNpr was microrecorded to ascertain the activity of thebasal ganglia output structure. The effect of SKF38393 orQuinpirole injection on the firing rate and firing patternsof SNpr was investigated in medial forebrain bundle (MFB)lesioned rats and in MFB+STN lesioned rats.Theadministration of SKF38393 decreased SNpr neuronal firingrates and the percentage of burst neurons in the MFBlesioned rats, but did not alter them in MFB+STN lesionedrats. The administration ofQuinpirole significantlydecreased the spontaneous firing rate in the MFB lesionedrats. However, after an additional STN lesion, it increasedthe percentage of burst neurons.This study demonstratedthat dopamine agonists and STN lesion decreased thehyperactive firing rate and the percentage of burst neuronsof SNpr neurons in 6-OHDA lesioned rats, respectively.Quinpirole with STN lesion increased a percentage of burstneurons. To clear the exact interactive mechanism of D(1)and D(2) agonist and the corresponding location, it shouldbe followed a study using a nonselective dopamine agonistand D(1), D(2) selective antagonist.