Conditional neural knockout of the adenosine A2A receptor and pharmacological A2A antagonism reduce pilocarpine-induced tremulous jaw movements: Studies with a mouse model of parkinsonian tremor
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Otros documentos de la autoría: Salamone, John; Collins-Praino, Lyndsey E.; Pardo Andrés, Marta; Podurgiel, Samantha J.; Baqi, Younis; Müller, Christa E.; Schwarzschild, Michael A.; Correa, Merce
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Título
Conditional neural knockout of the adenosine A2A receptor and pharmacological A2A antagonism reduce pilocarpine-induced tremulous jaw movements: Studies with a mouse model of parkinsonian tremorAutoría
Fecha de publicación
2013Editor
ElsevierISSN
0924-977X; 1873-7862Cita bibliográfica
European Neuropsychopharmacology Volume 23, Issue 8, August 2013, Pages 972–977Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
http://www.sciencedirect.com/science/article/pii/S0924977X12002222Palabras clave / Materias
Resumen
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 ... [+]
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 (0.25–1.0 mg/kg IP). These movements occurred largely in the 3–7.5 Hz local frequency range. Administration of the adenosine A2A antagonist MSX-3 (2.5–10.0 mg/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. [-]
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European Neuropsychopharmacology, 2013, vol. 23, no 8Derechos de acceso
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