title: Conditional neural knockout of the adenosine A(2A) receptor and pharmacological A(2A) antagonism reduce pilocarpine-induced tremulous jaw movements: studies with a mouse model of parkinsonian tremor.
abstract: Tremulous jaw movements are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rats, tremulous jaw movements can be induced by a number of conditions that parallel those seen in human parkinsonism, including dopamine depletion, dopamine antagonism, and cholinomimetic drugs. Moreover, tremulous jaw movements in rats can be attenuated using antiparkinsonian agents such as L-DOPA, dopamine agonists, muscarinic antagonists, and adenosine A(2A) antagonists. In the present studies, a mouse model of tremulous jaw movements was established to investigate the effects of adenosine A(2A) antagonism, and a conditional neuronal knockout of adenosine A(2A) receptors, on cholinomimetic-induced tremulous jaw movements. The muscarinic agonist pilocarpine significantly induced tremulous jaw movements in a dose-dependent manner (0.25-1.0mg/kg IP). These movements occurred largely in the 3-7.5 Hz local frequency range. Administration of the adenosine A(2A) antagonist MSX-3 (2.5-10.0 mg/kg IP) significantly attenuated pilocarpine-induced tremulous jaw movements. Furthermore, adenosine A(2A) receptor knockout mice showed a significant reduction in pilocarpine-induced tremulous jaw movements compared to littermate controls. These results demonstrate the feasibility of using the tremulous jaw movement model in mice, and indicate that adenosine A(2A) receptor antagonism and deletion are capable of reducing cholinomimetic-induced tremulous jaw movements in mice. Future studies should investigate the effects of additional genetic manipulations using the mouse tremulous jaw movement model.
authors.affiliation: Behavioral Neuroscience Division, Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA. john.salamone@uconn.edu
authors.forename: John D
authors.initials: JD
authors.lastname: Salamone
authors.forename: Lyndsey E
authors.initials: LE
authors.lastname: Collins-Praino
authors.forename: Marta
authors.initials: M
authors.lastname: Pardo
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Podurgiel
authors.forename: Younis
authors.initials: Y
authors.lastname: Baqi
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schwarzschild
authors.forename: Mercè
authors.initials: M
authors.lastname: Correa
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007568:Jaw; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D010862:Pilocarpine; D011355:Prodrugs / Q000627:therapeutic use; D011897:Random Allocation; D043705:Receptor, Adenosine A2A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014202:Tremor / Q000209:etiology / Q000517:prevention & control*; D014970:Xanthines / Q000627:therapeutic use
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; C113602:MSX 3 compound; D009419:Nerve Tissue Proteins; D011355:Prodrugs; D043705:Receptor, Adenosine A2A; D014970:Xanthines; D010862:Pilocarpine