Rodent Models of Tremor

Overview

Journal Cerebellum

Publisher Springer

Specialty Neurology

Date 2007 Mar 17

PMID 17366267

Citations 46

Authors

Hideto Miwa

Affiliations

Soon will be listed here.

Abstract

This review focuses on rodent models of tremor, particularly those induced by pharmacological agents. Harmaline is one of the most frequently used tremor-generating drugs and harmaline-induced tremor is regarded as a model of essential tremor. Harmaline acts on inferior olive neurons, causing enhanced neuronal synchrony and rhythmicity in the olivocerebellar system. In addition, it selectively induces cerebellar Purkinje cell death, speculatively because of excessive glutamate release from nerve terminals of the olivocerebellar system onto Purkinje cells. Systemic administration of cholinomimetics can also produce generalized tremor, and muscarinic receptors on striatal neurons are thought to be the best candidate for the tremor-generating mechanism. On the other hand, dopaminergic neurotoxins, which are used in models of parkinsonism, have yet to be used for experimental analysis of tremor, because tremors induced by dopamine depletion in rodents are less remarkable than those induced by harmaline or cholinomimetics. Recently developed gamma-aminobutyric acid (GABA)(A) receptor alpha-1 subunit knockout mice exhibit postural and kinetic tremors, and clearly reproduce the features of essential tremors. Although from a phenomenological point of view, rodent models of tremor cannot entirely mimic human tremor disorders, they have useful advantages in the analysis of pathophysiological mechanisms underlying tremor. Development of convenient and reproducible methods for evaluating rodent tremor is therefore recommended.

Citing Articles

Tremor in the Age of Omics: An Overview of the Transcriptomic Landscape of Essential Tremor.

Aboasali F, Castonguay C, Medeiros M, Dion P, Rouleau G Cerebellum. 2025; 24(2):35.

PMID: 39853640 DOI: 10.1007/s12311-025-01793-3.

Mapping Pharmacologically Evoked Neurovascular Activation and Its Suppression in a Rat Model of Tremor Using Functional Ultrasound: A Feasibility Study.

Nayak R, Lee J, Sotoudehnia S, Chang S, Fatemi M, Alizad A Sensors (Basel). 2023; 23(15).

PMID: 37571686 PMC: 10422538. DOI: 10.3390/s23156902.

GABA-A Alpha 2/3 but Not Alpha 1 Receptor Subunit Ligand Inhibits Harmaline and Pimozide-Induced Tremor in Rats.

Kosmowska B, Paleczna M, Biala D, Kadluczka J, Wardas J, Witkin J Biomolecules. 2023; 13(2).

PMID: 36830567 PMC: 9953228. DOI: 10.3390/biom13020197.

T-type calcium channels as therapeutic targets in essential tremor and Parkinson's disease.

Matthews L, Puryear C, Correia S, Srinivasan S, Belfort G, Pan M Ann Clin Transl Neurol. 2023; 10(4):462-483.

PMID: 36738196 PMC: 10109288. DOI: 10.1002/acn3.51735.

Three Naturally-Occurring Psychedelics and Their Significance in the Treatment of Mental Health Disorders.

Vorobyeva N, Kozlova A Front Pharmacol. 2022; 13:927984.

PMID: 35837277 PMC: 9274002. DOI: 10.3389/fphar.2022.927984.

References

Speelman J, Schuurman R, de Bie R, Esselink R, Bosch D . Stereotactic neurosurgery for tremor. Mov Disord. 2002; 17 Suppl 3:S84-8. DOI: 10.1002/mds.10147. View

Stern P, Radovic N, Buljubasic S . Pharmacology of experimental tremor. Nature. 1965; 206(990):1261. DOI: 10.1038/2061261a0. View

Milner T, CADORET G, Lessard L, Smith A . EMG analysis of harmaline-induced tremor in normal and three strains of mutant mice with Purkinje cell degeneration and the role of the inferior olive. J Neurophysiol. 1995; 73(6):2568-77. DOI: 10.1152/jn.1995.73.6.2568. View

Kalaria R, Mitchell M, Harik S . Correlation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity with blood-brain barrier monoamine oxidase activity. Proc Natl Acad Sci U S A. 1987; 84(10):3521-5. PMC: 304903. DOI: 10.1073/pnas.84.10.3521. View

Cox B, Potkonjak D . An investigation of the tremorgenic effects of oxotremorine and tremorine after stereotaxic injection into rat brain. Int J Neuropharmacol. 1969; 8(3):291-7. DOI: 10.1016/0028-3908(69)90050-1. View

Batini C, Buisseret-Delmas C . Harmaline-induced tremor. I. Regional metabolic activity as revealed by [14C]2-deoxyglucose in cat. Exp Brain Res. 1981; 42(3-4):371-82. DOI: 10.1007/BF00237502. View

Gupta M, Gupta B, Thomas R, Bruemmer V, Sladek Jr J, Felten D . Aged mice are more sensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment than young adults. Neurosci Lett. 1986; 70(3):326-31. DOI: 10.1016/0304-3940(86)90573-2. View

Salamone J, Carlson B, Rios C, Lentini E, Correa M, Wisniecki A . Dopamine agonists suppress cholinomimetic-induced tremulous jaw movements in an animal model of Parkinsonism: tremorolytic effects of pergolide, ropinirole and CY 208-243. Behav Brain Res. 2004; 156(2):173-9. DOI: 10.1016/j.bbr.2004.05.019. View

Wang G, Fowler S . Concurrent quantification of tremor and depression of locomotor activity induced in rats by harmaline and physostigmine. Psychopharmacology (Berl). 2001; 158(3):273-80. DOI: 10.1007/s002130100882. View

10.

de Souza da Fonseca A, Pereira F, Santos R . Validation of a new computerized system for recording and analysing drug-induced tremor in rats. J Pharmacol Toxicol Methods. 2002; 46(3):137-43. DOI: 10.1016/s1056-8719(02)00169-7. View

11.

Ungerstedt U, LJUNGBERG T, Steg G . Behavioral, physiological, and neurochemical changes after 6-hydroxydopamine-induced degeneration of the nigro-striatal dopamine neurons. Adv Neurol. 1974; 5:421-6. View

12.

Suemaru K, Oishi R, Gomita Y . Characteristics of tail-tremor induced by nicotine in rats. Naunyn Schmiedebergs Arch Pharmacol. 1994; 350(2):153-7. DOI: 10.1007/BF00241090. View

13.

OHearn E, Molliver M . The olivocerebellar projection mediates ibogaine-induced degeneration of Purkinje cells: a model of indirect, trans-synaptic excitotoxicity. J Neurosci. 1997; 17(22):8828-41. PMC: 6573067. View

14.

Hamilton B, Smith D, Mueller K, Kerrebrock A, Bronson R, van Berkel V . The vibrator mutation causes neurodegeneration via reduced expression of PITP alpha: positional complementation cloning and extragenic suppression. Neuron. 1997; 18(5):711-22. DOI: 10.1016/s0896-6273(00)80312-8. View

15.

Miwa H, Kubo T, Suzuki A, Kihira T, Kondo T . A species-specific difference in the effects of harmaline on the rodent olivocerebellar system. Brain Res. 2006; 1068(1):94-101. DOI: 10.1016/j.brainres.2005.11.036. View

16.

Deng H, Xie W, Le W, Huang M, Jankovic J . Genetic analysis of the GABRA1 gene in patients with essential tremor. Neurosci Lett. 2006; 401(1-2):16-9. DOI: 10.1016/j.neulet.2006.02.066. View

17.

Wills A, Jenkins I, Thompson P, Findley L, Brooks D . Red nuclear and cerebellar but no olivary activation associated with essential tremor: a positron emission tomographic study. Ann Neurol. 1994; 36(4):636-42. DOI: 10.1002/ana.410360413. View

18.

Rothwell J . Physiology and anatomy of possible oscillators in the central nervous system. Mov Disord. 1998; 13 Suppl 3:24-8. DOI: 10.1002/mds.870131304. View

19.

Weimar W, Lane P, Sidman R . Vibrator (vb): a spinocerebellar system degeneration with autosomal recessive inheritance in mice. Brain Res. 1982; 251(2):357-64. DOI: 10.1016/0006-8993(82)90754-5. View

20.

Sugihara I, Lang E, Llinas R . Serotonin modulation of inferior olivary oscillations and synchronicity: a multiple-electrode study in the rat cerebellum. Eur J Neurosci. 1995; 7(4):521-34. DOI: 10.1111/j.1460-9568.1995.tb00657.x. View