Neuropharmacology 45 (2003) 1070–1079 www.elsevier.com/locate/neuropharm Noradrenaline increases the firing rate of a subpopulation of rat subthalamic neurones through the activation of α 1 -adrenoceptors Demetrio Arcos a,b , Arturo Sierra a , Alejandro Nun ˜ez a , Gonzalo Flores c , Jorge Aceves a , Jose ´-Antonio Arias-Montan ˜o a,* a Departamento de Fisiologı ´a, Biofı ´sica y Neurociencias, Centro de Investigacio ´n y de Estudios Avanzados (Cinvestav), Mexico, DF, Mexico b Escuela de Medicina Ignacio A. Santos, ITESM, Monterrey, Mexico c Instituto de Fisiologı ´a, Universidad Auto ´noma de Puebla, Puebla, Mexico Received 23 September 2002; received in revised form 8 July 2003; accepted 16 July 2003 Abstract In the rat subthalamic nucleus, which plays a critical role in the control of motor behaviour, specific binding of [ 3 H]-prazosin was detected by radioligand binding to homogenates and by autoradiography in slices. [ 3 H]-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 [ 3 H]-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.  2003 Elsevier Ltd. All rights reserved. Keywords: α 1 -adrenoceptor; Noradrenaline; Subthalamic nucleus; Basal ganglia; Neuronal firing; Catecholamine 1. Introduction The basal ganglia are a group of subcortical nuclei, complex and highly interconnected, intimately involved in the control of movement (Smith et al., 1998). In rod- ents the basal ganglia include the striatum, the globus pallidus (GP), the entopeduncular nucleus (EP), the sub- thalamic nucleus (STN) and the substantia nigra (Gerfen and Wilson, 1996; Smith et al., 1998; Bolam et al., 2000). The STN contains glutamatergic neurones that play a * Corresponding author. Tel.: +5255-5061-3964; fax: +5255- 5061-3754. E-mail address: jaarias@fisio.cinvestav.mx (J.-A. Arias- Montan ˜o). 0028-3908/$ - see front matter  2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0028-3908(03)00315-0 pivotal role in the regulation of basal ganglia output nuclei, namely the substantia nigra pars reticulata (SNr) and EP (Alexander and Crutcher, 1990; Parent and Hazrati, 1995; Smith et al., 1998), as inferred from clin- icopathological data from humans and experimental studies in animals (Bergman et al., 1990; DeLong, 1990). In particular, clinical evidence indicates that ball- ism, a severe form of dyskinesia, is usually associated with damage to STN or its synaptic circuitry (DeLong, 1990). By comparing electrophysiological in vitro and in vivo recordings, Overton and Greenfield (1995) have shown that the activity of STN neurones is under control of their synaptic afferents. This regulation appears to be mainly due to excitatory glutamatergic and inhibitory GABAergic inputs from the cerebral cortex and GP,