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.

Park, Yong Sook; Jeon, Mi Fa; Lee, Bae Hwan; Chang, Jin Woo

doi:2007.42.6.455

Original Article

Journal of Korean Neurosurgical Society 2007;42(6): 455-461.
doi: https://doi.org/10.3340/jkns.2007.42.6.455

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.

Yong Sook Park, Mi Fa Jeon, Bae Hwan Lee, Jin Woo Chang

¹Department of Neurosurgery, Chung-Ang University, College of Medicine, Seoul, Korea.
²Department of Neurosurgery, Brain Korea 21 Project for Medical Science, Yonsei University, College of Medicine, Seoul, Korea. jchang@yumc.yonsei.ac.kr
³Brain Research Institute, Yonsei University, College of Medicine, Seoul, Korea.

ABSTRACT

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.