Effects of dopamine D1 and D2 receptor antagonists on laryngeal neurophysiology in the rat.
Hypophonia is an early symptom in Parkinson's disease (PD) that involves an increase in laryngeal muscle activity, interfering with voice production. Our aim was to use an animal model to better understand the role of different dopamine receptor subtypes in the control of laryngeal neurophysiology. First, we evaluated the combined effects of SCH23390-a D(1) receptor antagonist with a D(2) receptor antagonist (eticlopride) on laryngeal neurophysiology, and then tested the separate effects of selective receptor antagonists. Thyroarytenoid (TA) and gastrocnemius (GN) muscle activity was measured at rest and while stimulating the internal branch of superior laryngeal nerve to elicit the laryngeal adductor response (LAR) in alpha-chloralose-anesthetized rats. Paired stimuli at different interstimulus intervals between 250 and 5,000 ms measured central conditioning of the LAR. Changes in resting muscle activity, response latency, amplitude, and LAR conditioning after each drug were compared with the saline control. SCH23390 alone increased the resting TA muscle activity (P < 0.05). With the combined SCH23390 + eticlopride or SCH23390 alone, response latency decreased (P < 0.01), amplitude increased (P < 0.01), and the test LAR was reduced at 2,000-ms ISI (P < 0.01). No LAR changes occurred when eticlopride was administered alone at a low dose and only a tendency to suppress responses was found at a high dose. No changes in GN muscle activity occurred in any of the groups. The results suggest that a loss of stimulation of D(1) receptors plays a significant role in laryngeal pathophysiology in PD.
Feng
Xin
X
Laryngeal and Speech Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1416, USA.
Henriquez
Victor M
VM
Walters
Judith R
JR
Ludlow
Christy L
CL
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004576:Electromyography; D007818:Laryngeal Diseases / Q000503:physiopathology*; D007821:Laryngeal Muscles / Q000187:drug effects / Q000503:physiopathology*; D007823:Laryngeal Nerves / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012457:Salicylamides / Q000494:pharmacology; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D012457:Salicylamides; C045989:eticlopride