Abstract
Animal behaviours that are easy to measure make great test systems for drug development, but we sometimes neglect to try to understand how their four-legged world view translates to our own. In this brief essay, I try to relate the turning behaviour that has been so useful in the development of drugs that act on Parkinsonian symptoms to the actual symptoms themselves. The thoughts led to a couple of predictions about Parkinsonian behaviour that help to link the bradykinesia that both patients and animals show. In conclusion, I suggest the general idea that dopamine acts to facilitate the learning and expression of the predicted outcomes of simple motor acts: perhaps as a different expression of the reward prediction for which dopamine is already thought to be important.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Fox SH, Brotchie JM. The MPTP-lesioned non-human primate models of Parkinson’s disease. Past, present, and future. In: Bjorklund A, Cenci MA (eds). Progress in Brain Research. Amsterdam: Elsevier; 2010. pp. 133–157.
Ungerstedt U. Adipsia and Aphagia after 6-Hydroxdopamine induced Degeneration of the Nigro-striatal Dopamine System. Acta Physiol Scand Suppl 1971; 367: 95–122.
Ungerstedt U, Arbuthnott GW. Quantitative recording of rotational behaviour in rats after 6- hydroxy-dopamine lesions of the nigrostriatal dopamine system. Brain Research 1970; 24: 485–493.
Ingham CA, Hood SH, Taggart P, Arbuthnott GW. Plasticity of synapses in the rat neostriatum after unilateral lesion of the nigrostriatal dopaminergic pathway. Journal of Neuroscience 1998; 18: 4732–4743.
Stephens B, Mueller AJ, Shering AF, Hood SH, Taggart P, Arbuthnott GW et al. Evidence of a breakdown of corticostriatal connections in Parkinson’s disease. Neuroscience 2005; 132: 741–754.
Torres EM, Monville C, Gates MA, Bagga V, Dunnett SB. Improved survival of young donor age dopamine grafts in a rat model of Parkinson’s disease. Neuroscience 2007; 146: 1606–1617.
Tillerson JL, Cohen AD, Philhower J, Miller GW, Zigmond MJ, Schallert T. Forced limb-use effects on the behavioral and neurochemical effects of 6-hydroxydopamine. Journal of Neuroscience 2001; 21: 4427–4435.
Ugura-Okorie DC, Arbuthnott GW. Altered paw preference after unilateral 60hydroxydopamine injections into lateral hypothalamus. Neuropsychologia 1981; 19: 463–467.
Hamilton MH, Garcia-Munoz M, Arbuthnott GW. Separation of the motor consequences from other actions of unilateral 6-hydroxydopamine lesions in the nigrostriatal neurones of rat brain. Brain Research 1985; 348: 220–228.
Dunnett SB, Lelos M. Behavioural analysis of motor and non-motor symptoms in rodent models of Parkinson’s disease. In: Bjorklund A, Cenci MA (eds). Progress in Brain Research. Amsterdam: Elsevier; 2010. pp. 35–51.
Arbuthnott GW, Attree TJ, Eccleston D, Loose RW, Martin MJ. Is adenylate cyclase the dopamine receptor? Medical Biology 1974; 52: 350–353.
Damianopoulos EN, Carey RJ. Apomorphine sensitization effects: Evidence for environmentally contingent behavioral reorganization processes. Pharmacol Biochem Behav 1993; 45: 655–663.
Herrera-Marschitz M, Arbuthnott G, Ungerstedt U. The rotational model and microdialysis: Significance for dopamine signalling, clinical studies, and beyond. Progress in Neurobiology 2010; 90: 176–189.
Schultz W, Dickinson A. Neuronal coding of prediction errors. Annual Review of Neuroscience 2000; 23: 473–500.
Plotnik M, Giladi N, Hausdorff J. A new measure for quantifying the bilateral coordination of human gait: effects of aging and Parkinson’s disease. Experimental Brain Research 2007; 181: 561–570.
Plotnik M, Giladi N, Hausdorff JM. Bilateral coordination of gait and Parkinson’s disease: the effects of dual tasking. J Neurol Neurosurg Psychiatry 2009; 80: 347–350.
Plotnik M, Giladi N, Dagan Y, Hausdorff J. Postural instability and fall risk in Parkinson’s disease: impaired dual tasking, pacing, and bilateral coordination of gait during the “ON” medication state. Experimental Brain Research 2011: 1–10.
Martin JP. The Basal Ganglia and Posture. The Basal Ganglia and Posture. Philadelphia: Lippincott; 1965.
Grafton ST, Tunik E. Human Basal Ganglia and the Dynamic Control of Force during On-Line Corrections. Journal of Neuroscience 2011; 31: 1600–1605.
Kording KP, Wolpert DM. Bayesian integration in sensorimotor learning. Nature 2004; 427: 244–247.
Wing AM, Miller E. Basal ganglia lesions and psychological analyses of the control of voluntary movement. Ciba Foundation Symposium 1984; 107: 242–257.
Steiner H, Huston JP. Control of turning behavior under apomorphine by sensory input from the face. Psychopharmacology (Berl) 1992; 109: 390–394.
Sacks, O. Epilogue pp 284, Awakenings, Vintage Books, 1999.
Briand KA, Strallow D, Hening W, Poizner H, Sereno AB. Control of voluntary and reflexive saccades in Parkinson’s disease. Experimental Brain Research 1999; 129: 38–48.
Hodgson TL, Dittrich WH, Henderson L, Kennard C. Eye movements and spatial working memory in Parkinson’s disease. Neuropsychologia 1999; 37: 927–938.
Acknowledgements
Thanks for many readings of this text to Marianela Garcia-Munoz as well as for the encouragement to stay with handedness as a measure. Thanks too to Steve Dunnett – the only other person with whom I have really discussed this crazy idea.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Arbuthnott, G.W. (2011). Of Rats and Patients: Some Thoughts About Why Rats Turn in Circles and Parkinson’s Disease Patients Cannot Move Normally. In: Lane, E., Dunnett, S. (eds) Animal Models of Movement Disorders. Neuromethods, vol 61. Humana Press. https://doi.org/10.1007/978-1-61779-298-4_16
Download citation
DOI: https://doi.org/10.1007/978-1-61779-298-4_16
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-297-7
Online ISBN: 978-1-61779-298-4
eBook Packages: Springer Protocols