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.
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 D(1) receptor agonist) and Quinpirole (a D(2) 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 ofQuinpirole significantly decreased the spontaneous firing rate in the MFB lesioned rats. However, after an additional STN lesion, it increased the percentage of burst neurons.


CONCLUSIONS
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 D(1) and D(2) agonist and the corresponding location, it should be followed a study using a nonselective dopamine agonist and D(1), D(2) selective antagonist.
Park
Yong Sook
YS
Department of Neurosurgery , Chung-Ang University, College of Medicine, Seoul, Korea.
Jeon
Mi Fa
MF
Lee
Bae Hwan
BH
Chang
Jin Woo
JW