Noradrenaline increases the firing rate of a subpopulation of rat subthalamic neurones through the activation of α 1-adrenoceptors

Abstract

In the rat subthalamic nucleus, which plays a critical role in the control of motor behaviour, specific binding of [ 3H]-prazosin was detected by radioligand binding to homogenates and by autoradiography in slices. [ 3H]-Prazosin binding to homogenates (B max 71±5 fmol/mg protein; K d 0.27±0.05 nM) was competed for by α 1-antagonists. In subthalamic nucleus slices and in the presence of 10 mM LiCl, noradrenaline (100 μM) produced a modest, but consistent, stimulation of [ 3H]-inositol phosphate accumulation (146±6% of basal), reversed by the α 1-antagonist prazosin (1 μM). Extracellular single-unit recordings in slices showed that in a subpopulation (61 out of 94 cells) of rat subthalamic neurones with regular, single-spike firing pattern, noradrenaline induced a concentration-dependent increase in the firing rate (EC 50 2.5±0.2 μM, maximum effect 272±33% of basal). The action of noradrenaline was mimicked by the selective α 1-agonist phenylephrine but not by selective α 2- or β-agonists, and was blocked by the α 1-antagonist prazosin but not by α 2- or β-antagonists. The excitatory effect of noradrenaline was not prevented by perfusion with low Ca 2+/high Mg 2+ solution. In four out of 11 neurones perfusion with 3 μM noradrenaline resulted in a shift from bursting to regular firing. Taken together, our results indicate that rat subthalamic neurones express α 1-adrenoceptors responsible for noradrenaline-induced stimulation of the firing rate of a subpopulation of neurones. By modulating the spontaneous activity of STN neurones, noradrenergic pathways might have a significant role in regulating basal ganglia function and thus motor activity.