Lesion of Subthalamic Nucleus in Parkinsonian Rats: Effects of Dopamine D1 and D2 Receptor Agonists on the Neuronal Activities of the Substantia Nigra Pars Reticulata

OBJECTIVE: It was hypothesized that dopamine agonist administration and subthalamic nucleus (STN) lesion in the rat might have a synergistic effect on the neuronal activities of substantia nigra pars reticulata (SNpr) as observed in patients with Parkinson's disease. The effects of SKF38393 (a D1 receptor agonist) and Quinpirole (a D2 receptor agonist) were compared in parkinsonian rat models with 6- hydroxydopamine (6-OHDA) after STN lesion. METHODS: SKF38393 and Quinpirole were consecutively injected intrastriatally. SNpr was microrecorded to ascertain the activity of the basal ganglia output structure. The effect of SKF38393 or Quinpirole injection on the firing rate and firing patterns of SNpr was investigated in medial forebrain bundle (MFB) lesioned rats and in MFB+STN lesioned rats. RESULTS: The administration of SKF38393 decreased SNpr neuronal firing rates and the percentage of burst neurons in the MFB lesioned rats, but did not alter them in MFB+STN lesioned rats. The administration of Quinpirole significantly decreased the spontaneous firing rate in the MFB lesioned rats. However, after an additional STN lesion, it increased the percentage of burst neurons. CONCLUSION: This study demonstrated that dopamine agonists and STN lesion decreased the hyperactive firing rate and the percentage of burst neurons of SNpr neurons in 6-OHDA lesioned rats, respectively. Quinpirole with STN lesion increased a percentage of burst neurons. To clear the exact interactive mechanism of D1 and D2 agonist and the corresponding location, it should be followed a study using a nonselective dopamine agonist and D1, D2 selective antagonist.

Alterations of Spontaneous Behaviors and the Neuronal Activities of the Deep Cerebral Nuclei by Subthalamic Lesion with Kainic Acid in Rat Parkinsonian Models with 6-hydroxydopamine

OBJECTIVE: The purpose of this study is to investigate the effect of ipsilateral subthalamic nucleus(STN) lesioning on the spontaneous behavioral changes and the alteration of neuronal activities of deep cerebral nuclei in the rat parkinsonian model with 6-hydroxydopamine(6-OHDA). METHODS: To identify the spontaneous behavioral changes, apomorphine-induced rotational test and forepaw adjusting step were performed. We subsequently investigated the alteration of neuronal activities in the substantia nigra pars reticulata(SNpr) and globus pallidus(GP), in order to compare them with the behavioral changes in rat parkinsonian models. RESULTS: The STN lesioning in the rat parkinsonian model clearly improved behavioral changes. Compared to the normal control rats, rat PD models exhibited a significant increase in mean firing rates and the percentage of bursting neurons in the STN and SNpr. In the STN-lesioned rat PD models, mean firing rates and the percentage of bursting neurons in the SNpr were reduced and those in the GP increased. CONCLUSION: STN lesioning induced behavior improvement in rat parkinsonian models seems to be consistent with the surgical outcomes of the STN stimulation therapy in advanced Parkinsonn's disease(PD). The alteration of the neuronal activities in the SNpr and GP suggests that these sites are responsible for the improvement of parkinsonian motor symptoms observed following STN lesioning in rat parkinsonian models. The significance of bursting activity in the SNpr and GP remains obscure. Further study is necessary to elucidate the pathophysiological mechanism of PD.