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

John D. Salamone, Lyndsey E. Collins-Praino, Marta Pardo, Samantha J. Podurgiel, Younis Baqi, Christa E. Müller, Michael A. Schwarzschild, Mercè Correa

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)972-977
Number of pages6
JournalEuropean Neuropsychopharmacology
Volume23
Issue number8
DOIs
Publication statusPublished - Aug 2013

Fingerprint

Adenosine A2A Receptors
Pilocarpine
Tremor
Jaw
Pharmacology
Adenosine
Cholinergic Agents
Dopamine
Drug Antagonism
Antiparkinson Agents
Muscarinic Agonists
Muscarinic Antagonists
Mastication
Dopamine Agonists
Parkinsonian Disorders
Knockout Mice

Keywords

  • Acetylcholine
  • Motor
  • Muscarinic receptor
  • Parkinson's disease
  • Parkinsonism
  • Striatum

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Biological Psychiatry
  • Neurology
  • Pharmacology

Cite this

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. / Salamone, John D.; Collins-Praino, Lyndsey E.; Pardo, Marta; Podurgiel, Samantha J.; Baqi, Younis; Müller, Christa E.; Schwarzschild, Michael A.; Correa, Mercè.

In: European Neuropsychopharmacology, Vol. 23, No. 8, 08.2013, p. 972-977.

Research output: Contribution to journalArticle

Salamone, John D. ; Collins-Praino, Lyndsey E. ; Pardo, Marta ; Podurgiel, Samantha J. ; Baqi, Younis ; Müller, Christa E. ; Schwarzschild, Michael A. ; Correa, Mercè. / 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. In: European Neuropsychopharmacology. 2013 ; Vol. 23, No. 8. pp. 972-977.
@article{b83117b1e6aa4a188d65938747d39bce,
title = "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",
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 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.",
keywords = "Acetylcholine, Motor, Muscarinic receptor, Parkinson's disease, Parkinsonism, Striatum",
author = "Salamone, {John D.} and Collins-Praino, {Lyndsey E.} and Marta Pardo and Podurgiel, {Samantha J.} and Younis Baqi and M{\"u}ller, {Christa E.} and Schwarzschild, {Michael A.} and Merc{\`e} Correa",
year = "2013",
month = "8",
doi = "10.1016/j.euroneuro.2012.08.004",
language = "English",
volume = "23",
pages = "972--977",
journal = "European Neuropsychopharmacology",
issn = "0924-977X",
publisher = "Elsevier",
number = "8",

}

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

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

VL - 23

SP - 972

EP - 977

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

IS - 8

ER -