title: Deep brain stimulation of the subthalamic nucleus reverses oral tremor in pharmacological models of parkinsonism: interaction with the effects of adenosine A2A antagonism.
abstract: Deep brain stimulation (DBS) of the subthalamic nucleus is increasingly being employed as a treatment for parkinsonian symptoms, including tremor. The present studies used tremulous jaw movements, a pharmacological model of tremor in rodents, to investigate the tremorolytic effects of subthalamic DBS in rats. Subthalamic DBS reduced the tremulous jaw movements induced by the dopamine D2 family antagonist pimozide and the D1 family antagonist ecopipam, as well as the cholinomimetics pilocarpine and galantamine. The ability of DBS to suppress tremulous jaw movements was dependent on the neuroanatomical locus being stimulated (subthalamic nucleus vs. a striatal control site), as well as the frequency and intensity of stimulation used. Importantly, administration of the adenosine A2A receptor antagonist MSX-3 reduced the frequency and intensity parameters needed to attenuate tremulous jaw movements. These results have implications for the clinical use of DBS, and future studies should determine whether adenosine A2A antagonism could be used to enhance the tremorolytic efficacy of subthalamic DBS at low frequencies and intensities in human patients.
authors.affiliation: Division of Behavioral Neuroscience, Department of Psychology, University of Connecticut, Storrs, CT, USA.
authors.forename: Lyndsey E
authors.initials: LE
authors.lastname: Collins-Praino
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Paul
authors.forename: Felicia
authors.initials: F
authors.lastname: Ledgard
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Podurgiel
authors.forename: Rotem
authors.initials: R
authors.lastname: Kovner
authors.forename: Younis
authors.initials: Y
authors.lastname: Baqi
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Senatus
authors.forename: John D
authors.initials: JD
authors.lastname: Salamone
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000633:toxicity*; D005702:Galantamine / Q000633:toxicity; D007568:Jaw / Q000294:innervation / Q000503:physiopathology; D008297:Male; D009068:Movement / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000628:therapy*; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000503:physiopathology*; D014202:Tremor / Q000139:chemically induced / Q000628:therapy*; D014970:Xanthines / Q000494:pharmacology*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D018492:Dopamine Antagonists; C113602:MSX 3 compound; D014970:Xanthines; D010862:Pilocarpine; D005702:Galantamine
keywords: Parkinson's disease; acetylcholine; dopamine; muscarinic; tremulous jaw movements