Content-Length: 381976 | pFad | https://doi.org/10.1080%2F14734220601016080

a=86400 Rodent models of tremor | The Cerebellum Skip to main content
Springer Nature Link
Log in

Rodent models of tremor

  • Mini-Review
  • Scientific Papers
  • Published:
The Cerebellum Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+
from $39.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Explore related subjects

Discover the latest articles, books and news in related subjects, suggested using machine learning.

References

  1. Martin FC, Thu Le A, Handforth A. Harmaline-induced tremor as a potential preclinical screening method for essential tremor medications. Mov Disord. 2005;20:298–305.

    Article  PubMed  Google Scholar 

  2. Yamazaki M, Tanaka C, Takaori S. Significance of central noradrenergic system on harmaline induced tremor. Pharmacol Biochem Behav. 1979;10:421–7.

    Article  PubMed  CAS  Google Scholar 

  3. Milner TE, Cadoret G, Lessard L, Smith AM. 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;73:2568–77.

    PubMed  CAS  Google Scholar 

  4. Lamarre Y, Mercier LA. Neurophysiological studies of harmaline-induced tremor in the cat. Can J Physiol Pharmacol. 1971;49:1049–58.

    PubMed  CAS  Google Scholar 

  5. Deuschl G, Elble RJ. The pathophysiology of essential tremor. Neurology. 2000;54(11 Suppl. 4):S14–20.

    PubMed  CAS  Google Scholar 

  6. Llinas R, Baker R, Sotelo C. Electrotonic coupling between neurons in cat inferior olive. J Neurophysiol. 1974;37: 560–71.

    PubMed  CAS  Google Scholar 

  7. Sugihara I, Lang EJ, Llinas R. Serotonin modulation of inferior olivary oscillations and synchronicity: A multipleelectrode study in the rat cerebellum. Eur J Neurosci. 1995;7:521–34.

    Article  PubMed  CAS  Google Scholar 

  8. De Montigny C, Lamarre Y. Effects produced by local applications of harmaline in the inferior olive. Can J Physiol Pharmacol. 1975;53:845–9.

    PubMed  Google Scholar 

  9. Simantov R, Snyder SH, Oster-Granite ML. Harmalineinduced tremor in the rat: Abolition by 3-acetylpyridine destruction of cerebellar climbing fibers. Brain Res. 1976; 114:144–51.

    Article  PubMed  CAS  Google Scholar 

  10. Batini C, Buisseret-Delmas C, Conrath-Verrier M. Olivocerebellar activity during harmaline-induced tremor.A 2- [14C]deoxyglucose study. Neurosci Lett. 1979;12:241–6.

    Article  PubMed  CAS  Google Scholar 

  11. Batini C, Buisseret-Delmas C, Conrath-Verrier M. Harmaline-induced tremor. I. Regional metabolic activity as revealed by [14C]2-deoxyglucose in cat. Exp Brain Res. 1981;42:371–82.

    Article  PubMed  CAS  Google Scholar 

  12. Miwa H, Nishi K, Fuwa T, Mizuno Y. Differential expression of c-fos following administration of two tremorgenic agents: Harmaline and oxotremorine. Neuroreport. 2000;11: 2385–90.

    Article  PubMed  CAS  Google Scholar 

  13. Lutes J, Lorden JF, Beales M, Oltmans GA. Tolerance to the tremorogenic effects of harmaline: Evidence for altered olivocerebellar function. Neuropharmacology. 1988;27:849–55.

    Article  PubMed  CAS  Google Scholar 

  14. Lorden JF, Stratton SE, Mays LE, Oltmans GA. Purkinje cell activity in rats following chronic treatment with harmaline. Neuroscience. 1988;27:465–72.

    Article  PubMed  CAS  Google Scholar 

  15. Miwa H, Kubo T, Suzuki A, Kihira T, Kondo T. A speciesspecific difference in the effects of harmaline on the rodent olivocerebellar system. Brain Res. 2006;1068:94–101.

    Article  PubMed  CAS  Google Scholar 

  16. O’Hearn E, Molliver ME. Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Neuroscience. 1993;55:303–10.

    Article  PubMed  CAS  Google Scholar 

  17. O’Hearn E, Molliver ME. The olivocerebellar projection mediates ibogaine-induced degeneration of Purkinje cells: A model of indirect, trans-synaptic excitotoxicity. J Neurosci. 1997;17:8828–41.

    PubMed  CAS  Google Scholar 

  18. Fowler SC, McKerchar TL, Zarcone HJ. Response dynamics: Measurement of the force and rhythm of motor responses in laboratory animals. In: LeDoux M, editor. Animal models of movement disorders. Burlington: Elsevier Academic Press, 2005. pp 73–100.

    Chapter  Google Scholar 

  19. Stern P, Radovic N, Buljubasic S. Pharmacology of experimental tremor. Nature. 1965;206:1261.

    Article  PubMed  CAS  Google Scholar 

  20. Hallberg H, Almgren O. Modulation of oxotremorineinduced tremor by central beta-adrenoceptors. Acta Physiol Scand. 1987;129:407–13.

    PubMed  CAS  Google Scholar 

  21. Cox B, Potkonjak D. An investigation of the tremorgenic effects of oxotremorine and tremorine after stereotaxic injection into rat brain. Int J Neuropharmacol. 1969;8:291–7.

    Article  PubMed  CAS  Google Scholar 

  22. Slater P, Dickinson SL. Effects of lesioning basal ganglia nuclei and output pathways on tremorine-induced tremor in rats. J Neurol Sci. 1982;57:235–47.

    Article  PubMed  CAS  Google Scholar 

  23. Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 1990;13:266–71.

    Article  PubMed  CAS  Google Scholar 

  24. Slater P. Effect of 6-hydroxydopamine on some actions of tremorine and oxotremorine. Eur J Pharmacol. 1974;25: 130–7.

    Article  PubMed  CAS  Google Scholar 

  25. Salamone JD, Mayorga AJ, Trevitt JT, Cousins MS, Conlan A, Nawab A. Tremulous jaw movements in rats: A model of parkinsonian tremor. Review. Prog Neurobiol. 1998;56:591–611.

    Article  CAS  Google Scholar 

  26. Salamone JD, Carlson BB, Rios C, Lentini E, Correa M, Wisniecki A, Betz 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. 2005;156: 173–9.

    Article  PubMed  CAS  Google Scholar 

  27. Suemaru K, Oishi R, Gomita Y. Characteristics of tail-tremor induced by nicotine in rats. Naunyn Schmiedebergs Arch Pharmacol. 1994;350:153–7.

    Article  PubMed  CAS  Google Scholar 

  28. Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidineanalog synthesis. Science. 1983;219:979–80.

    Article  PubMed  CAS  Google Scholar 

  29. Ballard PA, Tetrud JW, Langston JW. Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): Seven cases. Neurology. 1985;35:949–56.

    PubMed  CAS  Google Scholar 

  30. Kalaria RN, Mitchell MJ, Harik SI. Correlation of 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity with blood-brain barrier monoamine oxidase activity. Proc Natl Acad Sci USA. 1987;84:3521–5.

    Article  PubMed  CAS  Google Scholar 

  31. Gupta M, Gupta BK, Thomas R, Bruemmer V, Sladek JR Jr, Felten DL. Aged mice are more sensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment than young adults. Neurosci Lett. 1986;70:326–31.

    Article  PubMed  CAS  Google Scholar 

  32. Ungerstedt U, Ljungberg T, Steg G. Behavioral, physiological, and neurochemical changes after 6-hydroxydopamineinduced degeneration of the nigro-striatal dopamine neurons. AdvNeurol. 1974;5:421–6.

    CAS  Google Scholar 

  33. Buonamici M, Maj R, Pagani F, Rossi AC, Khazan N. Tremor at rest episodes in unilaterally 6-OHDA-induced substantia nigra lesioned rats: EEG-EMG and behavior. Neuropharmacology. 1986;25:323–5.

    Article  PubMed  CAS  Google Scholar 

  34. Jolicoeur FB, Rivest R, Drumheller A. Hypokinesia, rigidity, and tremor induced by hypothalamic 6-OHDA lesions in the rat. Brain Res Bull. 1991;26:317–20.

    Article  PubMed  CAS  Google Scholar 

  35. Suter U, Welcher AA, Ozcelik T, Snipes GJ, Kosaras B, Francke U, Billings-Gagliardi S, Sidman RL, Shooter EM. Trembler mouse carries a point mutation in a myelin gene. Nature. 1992;356:241–4.

    Article  PubMed  CAS  Google Scholar 

  36. Mikoshiba K, Yokoyama M, Inoue Y, Takamatsu K, Tsukada Y, Nomura T. Oligodendrocyte abnormalities in shiverer mouse mutant are determined in primary chimaeras. Nature. 1982;299:357–9.

    Article  PubMed  CAS  Google Scholar 

  37. Billings-Gagliardi S, Kirschner DA, Nadon NL, DiBenedetto LM, Karthigasan J, Lane P, Pearsall GB, Wolf MK. Jimpy 4J: A new X-linked mouse mutation producing severe CNS hypomyelination. Dev Neurosci. 1995;17:300–10.

    Article  PubMed  CAS  Google Scholar 

  38. Rehm S, Mehraein P, Anzil AP, Deerberg F. A new rat mutant with defective overhairs and spongy degeneration of the central nervous system: clinical and pathologic studies. Lab Anim Sci. 1982;32:70–3.

    PubMed  CAS  Google Scholar 

  39. Weimar WR, Lane PW, Sidman RL. Vibrator (vb): A spinocerebellar system degeneration with autosomal recessive inheritance in mice. Brain Res. 1982;251:357–64.

    Article  PubMed  CAS  Google Scholar 

  40. Hamilton BA, Smith DJ, Mueller KL, Kerrebrock AW, Bronson RT, van Berkel V, Daly MJ, Kruglyak L, Reeve MP, Nemhauser JL, Hawkins TL, Rubin EM, Lander ES. The vibrator mutation causes neurodegeneration via reduced expression of PITP alpha: Positional complementation cloning and extragenic suppression. Neuron. 1997;18: 711–22.

    Article  PubMed  CAS  Google Scholar 

  41. La Vail JH, Koo EH, Dekker NP. Motoneuron loss in the abducens nucleus of wobbler mice. Brain Res. 1987;404: 127–32.

    Article  Google Scholar 

  42. Tolbert DL, Ewald M, Gutting J, La Regina MC. Spatial and temporal pattern of Purkinje cell degeneration in shaker mutant rats with hereditary cerebellar ataxia. J Comp Neurol. 1995;355:490–507.

    Article  PubMed  CAS  Google Scholar 

  43. Kralic JE, Criswell HE, Osterman JL, O’Buckley TK, Wilkie ME, Matthews DB, Hamre K, Breese GR, Homanics GE, Morrow AL. Genetic essential tremor in gamma-aminobutyric acidA receptor alpha 1 subunit knockout mice. J Clin Invest. 2005;115:774–9.

    PubMed  CAS  Google Scholar 

  44. Wang G, Fowler SC. Concurrent quantification of tremor and depression of locomotor activity induced in rats by harmaline and physostigmine. Psychopharmacology (Berl). 2001;158:273–80.

    Article  CAS  Google Scholar 

  45. de Souza da Fonseca A, Pereira FR, Santos R. Validation of a new computerized system for recording and analyzing druginduced tremor in rats. J Pharmacol Toxicol Methods. 2001;46:137–43.

    Article  Google Scholar 

  46. Wilms H, Sievers J, Deuschl G. Animal models of tremor. MovDisord. 1999;14:557–71.

    Article  CAS  Google Scholar 

  47. Rappaport MS, Gentry RT, Schneider DR, Dole VP. Ethanol effects on harmaline-induced tremor and increase of cerebellar cyclic GMP. Life Sci. 1984;34:49–56.

    Article  PubMed  CAS  Google Scholar 

  48. Hallett M, Dubinsky RM. Glucose metabolism in the brain of patients with essential tremor. J Neurol Sci. 1993;114: 45–8.

    Article  PubMed  CAS  Google Scholar 

  49. Wills AJ, Jenkins IH, Thompson PD, Findley LJ, Brooks DJ. Red nuclear and cerebellar but no olivary activation associated with essential tremor: A positron emission tomographic study. Ann Neurol. 1994;36:636–42.

    Article  PubMed  CAS  Google Scholar 

  50. Speelman JD, Schuurman R, de Bie RM, Esselink RA, Bosch DA. Stereotactic neurosurgery for tremor. Mov Disord. 2002;17(Suppl. 3):S84–8.

    Article  PubMed  Google Scholar 

  51. Jankovic J, Noebels JL. Genetic mouse models of essential tremor: are they essential? J Clin Invest. 2005;115:584–6.

    Article  PubMed  CAS  Google Scholar 

  52. Deng H, Xie WJ, Le WD, Huang MS, Jankovic J. Genetic analysis of the GABRA1 gene in patients with essential tremor. Neurosci Lett. 2006;401:16–9.

    Article  PubMed  CAS  Google Scholar 

  53. Stolze H, Petersen G, Raethjen J, Wenzelburger R, Deuschl G. The gait disorder of advanced essential tremor. Brain. 2001;124:2278–86.

    Article  PubMed  CAS  Google Scholar 

  54. Duval C. Rest and postural tremors in patients with Parkinson’s disease. Brain Res Bull. 2006;70:44–8.

    Article  PubMed  Google Scholar 

  55. Bergman H, Deuschl G. Pathophysiology of Parkinson’s disease: From clinical neurology to basic neuroscience and back. Mov Disord. 2002;17(Suppl. 3):S28–40.

    Article  PubMed  Google Scholar 

  56. Plenz D, Kital ST. A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus. Nature. 1999;400:677–82.

    Article  PubMed  CAS  Google Scholar 

  57. Rothwell JC. Physiology and anatomy of possible oscillators in the central nervous system. Mov Disord. 1998;13(Suppl. 3):24–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-city, 641-8510, Wakayama, Japan

    Hideto Miwa MD

Authors
  1. Hideto Miwa MD
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Hideto Miwa MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miwa, H. Rodent models of tremor. Cerebellum 6, 66–72 (2007). https://doi.org/10.1080/14734220601016080

Download citation

  • Issue date:

  • DOI: https://doi.org/10.1080/14734220601016080

Key words









 ApplySandwichStrip

pFad - (p)hone/(F)rame/(a)nonymizer/(d)eclutterfier!      Saves Data!


--- a PPN by Garber Painting Akron. With Image Size Reduction included!

Fetched URL: https://doi.org/10.1080%2F14734220601016080

Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy