Apomorphine and dopamine D(1) receptor agonists increase the firing rates of subthalamic nucleus neurons.
The present study investigated the regulation of spontaneous neuronal activity in the subthalamic nucleus by dopamine receptors using in vivo extracellular single unit recording techniques. Subthalamic nucleus neuronal firing rates were doubled by systemic administration of the nonselective dopamine receptor agonist apomorphine. The response to apomorphine was attenuated in animals anesthetized with chloral hydrate or ketamine. The dopamine D(2)/D(3) receptor agonist quinpirole did not alter subthalamic nucleus neuronal firing rates. Firing rates were increased by the D(1) receptor agonists SKF 38393 and SKF 82958 two- to three-fold; these increases were reversed by the D(1) receptor antagonist, SCH 23390. Autoradiographic studies using [(125)I]SCH 23982 indicated that D(1) family receptors were located along the ventral edge of the subthalamic nucleus and the dorsal aspect of the cerebral peduncle. Local administration of SKF 82958 into the subthalamic nucleus doubled neuronal firing rates; these increases were reversed by systemic administration of SCH 23390. Infusion of SCH 23390 into the subthalamic nucleus prevented systemic SKF 38393 from increasing the firing rates of subthalamic nucleus neurons. These results indicate that apomorphine and D(1) receptor agonists exert an excitatory influence on subthalamic nucleus neuronal activity. In addition, the excitation induced by D(1) receptor agonists appears to be mediated, at least in part, by D(1) receptors located in the vicinity of the subthalamic nucleus. The data suggest that basal ganglia output under conditions of increased dopamine receptor stimulation is influenced by the activation of excitatory subthalamic efferent pathways, as opposed to suppression of these pathways as predicted by current models of basal ganglia function.
Kreiss
D S
DS
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA.
Anderson
L A
LA
Walters
J R
JR
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001345:Autoradiography; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013787:Thalamic Nuclei / Q000187:drug effects*
D018491:Dopamine Agonists; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001058:Apomorphine