Noradrenaline increases the firing rate of a subpopulation of rat subthalamic neurones through the activation of alpha 1-adrenoceptors.
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 (Bmax 71 +/- 5 fmol/mg protein; Kd 0.27 +/- 0.05 nM) was competed for by alpha1-antagonists. In subthalamic nucleus slices and in the presence of 10 mM LiCl, noradrenaline (100 microM) produced a modest, but consistent, stimulation of [3H]-inositol phosphate accumulation (146 +/- 6% of basal), reversed by the alpha1-antagonist prazosin (1 microM). 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 (EC50 2.5 +/- 0.2 microM, maximum effect 272 +/- 33% of basal). The action of noradrenaline was mimicked by the selective alpha1-agonist phenylephrine but not by selective alpha2- or beta-agonists, and was blocked by the alpha1-antagonist prazosin but not by alpha2- or beta-antagonists. The excitatory effect of noradrenaline was not prevented by perfusion with low Ca2+/high Mg2+ solution. In four out of 11 neurones perfusion with 3 microM noradrenaline resulted in a shift from bursting to regular firing. Taken together, our results indicate that rat subthalamic neurones express alpha1-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.
Arcos
Demetrio
D
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (Cinvestav), Mexico, DF, Mexico.
Sierra
Arturo
A
Nuñez
Alejandro
A
Flores
Gonzalo
G
Aceves
Jorge
J
Arias-Montaño
José Antonio
JA
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D058646:Adrenergic alpha-1 Receptor Agonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism / Q000502:physiology*; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000378:metabolism
D058646:Adrenergic alpha-1 Receptor Agonists; D018340:Receptors, Adrenergic, alpha-1; D009638:Norepinephrine; D011224:Prazosin