TY - JOUR
T1 - Oral tremor induced by galantamine in rats
T2 - A model of the parkinsonian side effects of cholinomimetics used to treat Alzheimer's disease
AU - Collins, Lyndsey E.
AU - Paul, Nicholas E.
AU - Abbas, Shams F.
AU - Leser, Chelsea E.
AU - Podurgiel, Samantha J.
AU - Galtieri, Daniel J.
AU - Chrobak, James J.
AU - Baqi, Younis
AU - Müller, Christa E.
AU - Salamone, John D.
N1 - Funding Information:
This research was supported by a grant to J. Salamone from the University of Connecticut Research Foundation , and a Life Sciences award to S. Abbas.
PY - 2011/9
Y1 - 2011/9
N2 - Anticholinesterases are the most common treatment for Alzheimer's disease, and, in recent years, a new group of cholinesterase inhibitors (i.e. rivastigmine, galantamine, and donepezil) has become available. Although these drugs improve cognitive symptoms, they also can induce or exacerbate parkinsonian symptoms, including tremor. The present studies were conducted to determine if galantamine induces tremulous jaw movements, a rodent model of parkinsonian tremor, and to investigate whether these oral motor impairments can be reversed by co-administration of adenosine A 2A antagonists. The first experiment demonstrated that systemic injections of galantamine (0.75-6.0 mg/kg I.P.) induced a dose-related increase in tremulous jaw movements in rats. In a second study, co-administration of the muscarinic antagonist scopolamine (0.0156-0.25 mg/kg I.P.) produced a dose dependent suppression of tremulous jaw movements induced by a 3.0 mg/kg dose of galantamine, indicating that galantamine induces these tremulous oral movements through actions on muscarinic acetylcholine receptors. In two additional studies, analyses of freeze-frame video and electromyographic activity recorded from the lateral temporalis muscle indicated that the local frequency of these galantamine-induced jaw movements occurs in the 3-7 Hz frequency range that is characteristic of parkinsonian tremor. In the final experiment, the adenosine A 2A antagonist MSX-3 significantly attenuated the tremulous jaw movements induced by the 3.0 mg/kg dose of galantamine, which is consistent with the hypothesis that co-administration of adenosine A 2A antagonists may be beneficial in reducing parkinsonian motor impairments induced by anticholinesterase treatment.
AB - Anticholinesterases are the most common treatment for Alzheimer's disease, and, in recent years, a new group of cholinesterase inhibitors (i.e. rivastigmine, galantamine, and donepezil) has become available. Although these drugs improve cognitive symptoms, they also can induce or exacerbate parkinsonian symptoms, including tremor. The present studies were conducted to determine if galantamine induces tremulous jaw movements, a rodent model of parkinsonian tremor, and to investigate whether these oral motor impairments can be reversed by co-administration of adenosine A 2A antagonists. The first experiment demonstrated that systemic injections of galantamine (0.75-6.0 mg/kg I.P.) induced a dose-related increase in tremulous jaw movements in rats. In a second study, co-administration of the muscarinic antagonist scopolamine (0.0156-0.25 mg/kg I.P.) produced a dose dependent suppression of tremulous jaw movements induced by a 3.0 mg/kg dose of galantamine, indicating that galantamine induces these tremulous oral movements through actions on muscarinic acetylcholine receptors. In two additional studies, analyses of freeze-frame video and electromyographic activity recorded from the lateral temporalis muscle indicated that the local frequency of these galantamine-induced jaw movements occurs in the 3-7 Hz frequency range that is characteristic of parkinsonian tremor. In the final experiment, the adenosine A 2A antagonist MSX-3 significantly attenuated the tremulous jaw movements induced by the 3.0 mg/kg dose of galantamine, which is consistent with the hypothesis that co-administration of adenosine A 2A antagonists may be beneficial in reducing parkinsonian motor impairments induced by anticholinesterase treatment.
KW - Acetylcholine
KW - Adenosine A2A
KW - Basal ganglia
KW - Muscarinic
KW - Parkinsonism
KW - Tremulous jaw movements
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U2 - 10.1016/j.pbb.2011.05.026
DO - 10.1016/j.pbb.2011.05.026
M3 - Article
C2 - 21640750
AN - SCOPUS:79958279401
SN - 0091-3057
VL - 99
SP - 414
EP - 422
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 3
ER -