TY - JOUR
T1 - Conditional neural knockout of the adenosine A2A receptor and pharmacological A2A antagonism reduce pilocarpine-induced tremulous jaw movements
T2 - Studies with a mouse model of parkinsonian tremor
AU - Salamone, John D.
AU - Collins-Praino, Lyndsey E.
AU - Pardo, Marta
AU - Podurgiel, Samantha J.
AU - Baqi, Younis
AU - Müller, Christa E.
AU - Schwarzschild, Michael A.
AU - Correa, Mercè
N1 - Funding Information:
This work was supported by grants to John Salamone from the University of Connecticut Research Foundation, which paid for all animals, supplies and equipment, except for the A 2A knockout mice and littermate controls, which were provided by a grant from Michael Schwarzschild from NIH (K24NS60991) and DoD (W81XWH-11-1-0150), Mercè Correa was supported by a grant from Fundació Bancaixa-UJI (P1.1B2010-43) and Caja Navarra, and Marta Pardo received a travel grant from Fundació Bancaixa-UJI.
Funding Information:
This work was supported by grants to John Salamone from the University of Connecticut Research Foundation , Michael Schwarzschild from NIH ( K24NS60991 ) and DoD ( W81XWH-11-1-0150 ), Mercè Correa from Fundació Bancaixa-UJI ( P1.1B2010-43 ) and Caja Navarra , and Marta Pardo from Fundació Bancaixa-UJI .
PY - 2013/8
Y1 - 2013/8
N2 - 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 A2A antagonists. In the present studies, a mouse model of tremulous jaw movements was established to investigate the effects of adenosine A2A antagonism, and a conditional neuronal knockout of adenosine A2A 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 3-7.5Hz local frequency range. Administration of the adenosine A2A antagonist MSX-3 (2.5-10.0mg/kg IP) significantly attenuated pilocarpine-induced tremulous jaw movements. Furthermore, adenosine A2A 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 A2A 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.
AB - 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 A2A antagonists. In the present studies, a mouse model of tremulous jaw movements was established to investigate the effects of adenosine A2A antagonism, and a conditional neuronal knockout of adenosine A2A 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 3-7.5Hz local frequency range. Administration of the adenosine A2A antagonist MSX-3 (2.5-10.0mg/kg IP) significantly attenuated pilocarpine-induced tremulous jaw movements. Furthermore, adenosine A2A 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 A2A 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.
KW - Acetylcholine
KW - Motor
KW - Muscarinic receptor
KW - Parkinson's disease
KW - Parkinsonism
KW - Striatum
UR - http://www.scopus.com/inward/record.url?scp=84881664456&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881664456&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2012.08.004
DO - 10.1016/j.euroneuro.2012.08.004
M3 - Article
C2 - 22947264
AN - SCOPUS:84881664456
SN - 0924-977X
VL - 23
SP - 972
EP - 977
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 8
ER -