Effects of intrasubthalamic injection of dopamine receptor agonists on subthalamic neurons in normal and 6-hydroxydopamine-lesioned rats: an electrophysiological and c-Fos study

Abstract

Subthalamic neuronal activity is controlled by a dopaminergic innervation, which may act via D1 and D2 dopamine receptors. This study investigates the effect of apomorphine and the selective D1 and D2 agonists, SKF 82958 and quinpirole respectively, in normal and 6-hydroxydopamine-lesioned rats. The effect of microinjection of these drugs into the subthalamic nucleus was assessed by recording unit activity and the expression of the c-Fos-immunoreactive protein in the subthalamic nucleus. Dopaminergic agonists reduced the discharge rate and did not induce c-Fos expression in the normal rat. Apomorphine and quinpirole increased the discharge rate and induced a strong expression of c-Fos-like immunoreactive proteins, whereas SKF 82958 induced a decrease of the discharge rate and a slight expression of c-Fos in 6-hydroxydopamine-lesioned rats. The striking contrast in the changes obtained with apomorphine and quinpirole in normal and 6-hydroxydopamine-lesioned rats is discussed in relation to a hyperexpression of D2 dopaminergic receptors on the GABAergic terminals into the subthalamic nucleus. These results show that, in normal rats, dopamine agonists exert an inhibitory control on subthalamic neurons via D1 and D2 receptors. However, in 6-hydroxydopamine-lesioned rats, the hyperactivity of subthalamic neurons is also reduced by D1 receptor agonist but not by D2 dopamine agonists. This last result points out one aspect of the complex mechanisms underlying the physiopathology of Parkinson's disease.