Induction of oral tremor in mice by the acetylcholinesterase inhibitor galantamine: Reversal with adenosine A2A antagonism

Samantha J Podurgiel; Tiahna Spencer; Rotem Kovner; Younis Baqi; Christa E Müller; Merce Correa; John D Salamone

doi:10.1016/j.pbb.2015.10.008

Induction of oral tremor in mice by the acetylcholinesterase inhibitor galantamine: Reversal with adenosine A2A antagonism

Pharmacol Biochem Behav. 2016 Jan:140:62-7. doi: 10.1016/j.pbb.2015.10.008. Epub 2015 Oct 13.

Authors

Samantha J Podurgiel¹, Tiahna Spencer¹, Rotem Kovner¹, Younis Baqi², Christa E Müller³, Merce Correa⁴, John D Salamone⁵

Affiliations

¹ Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
² Department of Chemistry, Faculty of Science, Sultan Qaboos University, P.O. Box 36, Postal Code 123 Muscat, Oman; Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie, Universität Bonn, Bonn, Germany.
³ Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie, Universität Bonn, Bonn, Germany.
⁴ Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA; Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12071 Castelló, Spain.
⁵ Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA. Electronic address: john.salamone@uconn.edu.

PMID: 26459156
DOI: 10.1016/j.pbb.2015.10.008

Abstract

Tremulous jaw movements (TJMs) have become a commonly used rat model of Parkinsonian tremor. TJMs can be induced by a number of neurochemical conditions that parallel those seen in human Parkinsonism, including DA depletion, DA antagonism, and cholinomimetic administration, and can be reduced by various antiparkinsonian agents. TJMs typically occur in bursts with the peak frequency in the range of 3-7.5 Hz, which is similar to the Parkinsonian tremor frequency range. While the vast majority of this work has been done using rats, current efforts have focused on extending the TJM model to mice. The aim of the present studies was to establish a mouse model of Parkinsonian resting tremor using the anticholinesterase galantamine, and to investigate the effects of adenosine A2A antagonism on galantamine-induced TJMs. Galantamine significantly induced TJMs in a dose-dependent manner (0.5, 1.0, 1.5, 2.0, 2.5 mg/kg IP). The TJMs tended to occur in bursts in the 3-7.5 Hz frequency range, with a peak frequency of approximately 6 Hz. Systemic administration of the adenosine A2A antagonist MSX-3 (2.5, 5.0, 10.0 mg/kg) significantly attenuated galantamine-induced TJMs. Co-administration of MSX-3 also altered the local frequency of galantamine-induced TJMs, decreasing the peak frequency from approximately 6 Hz to 5 Hz, though the vast majority of TJMs remained in the frequency range characteristic of Parkinsonian resting tremor. These results indicate that adenosine A2A antagonism is capable of reducing anticholinesterase-induced TJMs in mice. Extending the TJM model to mice gives researchers an additional avenue for investigating drug-induced Parkinsonism and tremorogenesis, and could be a useful addition to the study of motor abnormalities observed in mouse genetic models of Parkinsonism.

Keywords: Acetylcholine; Basal ganglia; Parkinson's disease; Parkinsonism; Striatum; Tremulous jaw movements.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine A2 Receptor Antagonists / therapeutic use*
Animals
Cholinesterase Inhibitors*
Dose-Response Relationship, Drug
Galantamine*
Jaw
Male
Mice
Mice, Inbred C57BL
Movement / drug effects
Parkinson Disease, Secondary / chemically induced*
Parkinson Disease, Secondary / drug therapy*
Parkinson Disease, Secondary / psychology
Receptor, Adenosine A2A / drug effects*
Tremor / chemically induced*
Tremor / drug therapy*
Xanthines / therapeutic use

Substances

Adenosine A2 Receptor Antagonists
Cholinesterase Inhibitors
MSX 3 compound
Receptor, Adenosine A2A
Xanthines
Galantamine