title: Topography of dyskinesias and torticollis evoked by inhibition of substantia nigra pars reticulata.
abstract: GABAergic neurons of the substantia nigra pars reticulata (SNpr) and globus pallidus pars interna (GPi) constitute the output pathways of the basal ganglia. In monkeys, choreiform limb dyskinesias have been described after inhibition of the GPi, but not the SNpr. Given the anatomical and functional similarities between these structures, we hypothesized that choreiform dyskinesias could be evoked by inhibition of an appropriate region within the SNpr. The GABAA receptor agonist, muscimol, was infused into various sites within the SNpr and the adjacent STN of freely moving macaques. The effect of the GABAA antagonist, bicuculline (BIC), was also examined. Muscimol (MUS) in SNpr evoked the following: (1) choreiform dyskinesias of the contralateral arm and/or leg from central and lateral sites; (2) contralaterally directed torticollis from central and posterior sites; and (3) contraversive quadrupedal rotation from anterior and lateral sites. MUS infusions into the adjacent SN pars compacta or STN were without effect, ruling out a contribution of drug spread to adjacent structures. BIC in SNpr induced ipsiversive postures without choreiform dyskinesia or torticollis, whereas in the STN, it evoked ballistic movements. This is the first report of choreiform dyskinesia evoked by inhibition of the SNpr. This highly site-specific effect was obtained from a restricted region within the SNpr distinct from that responsible for inducing torticollis. These results suggest that overactivity of different SNpr outputs mediates choreiform dyskinesia and torticollis. These abnormalities are symptoms of dystonia, Huntington's disease, and iatrogenic dyskinesias, suggesting that these conditions may result, in part, from a loss of function in SNpr efferent projections.
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: David
authors.initials: D
authors.lastname: Dybdal
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Forcelli
authors.forename: Mark
authors.initials: M
authors.lastname: Dubach
authors.forename: Michael
authors.initials: M
authors.lastname: Oppedisano
authors.forename: Angela
authors.initials: A
authors.lastname: Holmes
authors.forename: Ludise
authors.initials: L
authors.lastname: Malkova
authors.forename: Karen
authors.initials: K
authors.lastname: Gale
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects; D020820:Dyskinesias / Q000378:metabolism*; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000187:drug effects / Q000502:physiology; D008251:Macaca; D009068:Movement / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000502:physiology; D014103:Torticollis / Q000139:chemically induced
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D009118:Muscimol