Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 38, Issue 1, Pages 2183-2191Publisher
WILEY
DOI: 10.1111/ejn.12212
Keywords
acetylcholine; dopamine; muscarinic; Parkinson's disease; tremulous jaw movements
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Funding
- University of Connecticut Health Center
- University of Connecticut Research Foundation
- Hoffman LaRoche
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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 D-2 family antagonist pimozide and the D-1 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 A(2A) 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 A(2A) antagonism could be used to enhance the tremorolytic efficacy of subthalamic DBS at low frequencies and intensities in human patients.
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