Skip to main content

Rotation in the 6-OHDA-Lesioned Rat

  • Protocol
  • First Online:

Part of the book series: Neuromethods ((NM,volume 61))

Abstract

Rotation is one of the most widely used tests in behavioural neuroscience. It is designed to detect motor turning and side biases in animals with lesions of basal ganglia circuits of the brain, and most notably ­following unilateral dopamine-depleting 6-OHDA lesions of the nigrostriatal bundle. When activated by stimulant or dopamine agonist drugs, rats and mice turn vigorously in circles for the duration of drug activity, yielding a reliable and easily quantifiable measure of the extent of the lesion and mechanism of drug action on the unbalanced dopamine system in the host brain. The design of automated rotometer test apparatus is discussed in detail, with advice for selecting the features most appropriate for different experimental applications. The selection of drugs, doses, time frames and testing protocols are then described, again in terms of the general principles that are readily adapted to particular experimental applications. Finally, a series of notes consider frequently asked questions related to practical issues involving drug selection, drug sensitisation, multiple testing and test spacing, and theoretical issues related to why and how does an animal rotate, and conditioning effects on the rotation response.

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

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Dunnett SB (2005) Motor functions of the nigrostriatal dopamine system: studies of lesions and behaviour. In: Dunnett SB, Bentivoglio M, Björklund A, Hökfelt T (eds) Handbook of Chemical Neuroanatomy. Vol. 21. Dopamine. Elsevier, pp 235–299

    Google Scholar 

  2. Andén N-E, Dahlström A, Fuxe K, Larsson K (1966) Functional role of the nigro-neostriatal dopamine neurons. Acta Pharmacol. Toxicol. 24: 263–274

    Article  Google Scholar 

  3. Ungerstedt U, Arbuthnott GW (1970) Quanti­tative recording of rotational behaviour in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res. 24: 485–493

    Article  PubMed  CAS  Google Scholar 

  4. Ungerstedt U (1971) Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour. Acta Physiol. Scand. suppl. 367: 49–68

    PubMed  CAS  Google Scholar 

  5. Glick SD, Jerussi TP, Fleisher LN (1976) Turning in circles: the neuropharmacology of rotation. Life Sci. 18: 889–896

    Article  PubMed  CAS  Google Scholar 

  6. Pycock CJ (1980) Turning behaviour in animals. Neuroscience 5: 461–514

    Article  PubMed  CAS  Google Scholar 

  7. Ungerstedt U, Butcher LL, Butcher SG, Andén N-E, Fuxe K (1969) Direct chemical stimulation of dopaminergic mechanisms of the neostriatum of the rat. Brain Res. 14: 461–471

    Article  PubMed  CAS  Google Scholar 

  8. Björklund A, Dunnett SB, Stenevi U, Lewis ME, Iversen SD (1980) Reinnervation of the denervated striatum by substantia nigra transplants: functional consequences as revealed by pharmacological and sensorimotor testing. Brain Res. 199: 307–333

    Article  PubMed  Google Scholar 

  9. Schwarz RD, Stein JW, Bernard P (1978) Rotometer for recording rotation in chemically or electrically stimulated rats. Physiol. Behav. 20: 351–354

    Article  PubMed  CAS  Google Scholar 

  10. Jerussi TP (1982) A simple, inexpensive rotometer for automatically recording the dynamics of circling behavior. Pharmacol. Biochem. Behav. 16: 353–357

    Article  PubMed  CAS  Google Scholar 

  11. Kehinde LO, Buraimoh-Igbo LA, Ude OU, Makanjuola RO (1984) Electronic rotameter for quantitative evaluation of rotational behaviour in rats after unilateral lesions of the nigrostriatal dopamine system. Med. Biol. Eng. Comput. 22: 361–366

    Article  PubMed  CAS  Google Scholar 

  12. Hudson JL, Levin DR, Hoffer BJ (1993) A 16-channel automated rotometer system for reliable measurement of turning behavior in 6-hydroxydopamine lesioned and transplanted rats. Cell Transplant. 2: 507–514

    PubMed  CAS  Google Scholar 

  13. Heredia-Lopez FJ, Bata-Garcia JL, Alvarez-Cervera FJ, Gongora-Alfaro JL (2002) A novel rotometer based on a RISC microcontroller. Behav. Res. Methods Instrum. Comput. 34: 399–407

    Article  PubMed  CAS  Google Scholar 

  14. Lane EL, Dunnett SB (2010) Pretreatment with dopamine agonists influence L-dopa mediated rotations without affecting abnormal involuntary movements in the 6-OHDA lesioned rat. Behav. Brain Res. 213: 66–72

    Article  PubMed  CAS  Google Scholar 

  15. Brooks SP, Dunnett SB (2009) Tests to assess motor phenotype in mice: a user’s guide. Nat. Rev. Neurosci. 10: 519–529

    Article  PubMed  CAS  Google Scholar 

  16. Pycock C, Tarsy D, Marsden CD (1975) Inhibition of circling behavior by neuroleptic drugs in mice with unilateral 6-hydroxydopamine lesions of the striatum. Psychopharmacologia 45: 211–219

    Article  PubMed  CAS  Google Scholar 

  17. Grealish S, Mattsson B, Draxler P, Björklund A (2010) Characterisation of behavioural and neurodegenerative changes induced by intranigral 6-hydroxydopamine lesions in a mouse model of Parkinson’s disease. Eur. J. Neurosci. 31: 2266–2278

    Article  PubMed  Google Scholar 

  18. Ungerstedt U (1976) 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine pathway: the turning syndrome. Pharmacol. Ther. B 2: 37–40

    PubMed  CAS  Google Scholar 

  19. Ungerstedt U (1971) Postsynaptic supersensitivity after 6-hydroxydopamine-induced degeneration of the nigro-striatal dopamine system. Acta Physiol. Scand. suppl. 367: 69–93

    PubMed  CAS  Google Scholar 

  20. Heikkila RE, Shapiro BS, Duvoisin RC (1981) The relationship between loss of dopamine nerve terminals, striatal (3H)spiroperidol binding and rotational behavior in unilaterally 6-hydroxydopamine-lesioned rats. Brain Res. 211: 285–292

    Article  PubMed  CAS  Google Scholar 

  21. Costall B, Marsden CD, Naylor RJ, Pycock CJ (1976) The relationship between striatal and mesolimbic dopamine dysfunction and the nature of circling responses following 6-hydroxydopamine and electrolytic lesions of the ascending dopamine systems of rat brain. Brain Res. 118: 87–113

    Article  PubMed  CAS  Google Scholar 

  22. Dunnett SB, Hernandez TD, Summerfield A, Jones GH, Arbuthnott GW (1988) Graft-derived recovery from 6-OHDA lesions: specificity of ventral mesencephalic graft tissues. Exp. Brain Res. 71: 411–424

    Article  PubMed  CAS  Google Scholar 

  23. Hefti F, Melamed E, Sahakian BJ, Wurtman RJ (1980) Circling behavior in rats with partial, unilateral nigro-striatal lesions: effects of amphetamine, apomorphine, and DOPA. Pharmacol. Biochem. Behav. 12: 185–188

    Article  PubMed  CAS  Google Scholar 

  24. Schmidt RH, Björklund A, Stenevi U, Dunnett SB, Gage FH (1983) Intracerebral grafting of neuronal cell suspensions. III. Activity of intrastriatal nigral suspension implants as assessed by measurements of dopamine synthesis and metabolism. Acta Physiol. Scand. suppl. 522: 19–28

    CAS  Google Scholar 

  25. Zigmond MJ, Abercrombie ED, Berger TW, Grace AA, Stricker EM (1990) Compensations after lesions of central dopaminergic neurons: some clinical and basic implications. Trends Neurosci. 13: 290–296

    Article  PubMed  CAS  Google Scholar 

  26. Kelly PH, Moore KE (1976) Mesolimbic dopaminergic neurones in the rotational model of nigrostriatal function. Nature 263: 695–696

    Article  PubMed  CAS  Google Scholar 

  27. Carli M, Evenden JL, Robbins TW (1985) Depletion of unilateral striatal dopamine impairs initiation of contralateral actions and not ­sensory attention. Nature 313: 679–682

    Article  PubMed  CAS  Google Scholar 

  28. Koshikawa N (1994) Role of the nucleus accumbens and the striatum in the production of turning behaviour in intact rats. Rev. Neurosci. 5: 331–346

    Article  PubMed  CAS  Google Scholar 

  29. Brown VJ, Dunnett SB (1989) Comparison of adrenal and fetal nigral grafts on drug-induced rotation in rats with 6-OHDA lesions. Exp. Brain Res. 78: 214–218

    Article  PubMed  CAS  Google Scholar 

  30. Annett LE, Reading PJ, Tharumaratnam D, Abrous DN, Torres EM, Dunnett SB (1993) Conditioning versus priming of dopaminergic grafts by amphetamine. Exp. Brain Res. 93: 46–54

    Article  PubMed  CAS  Google Scholar 

  31. Carey RJ (1986) Conditioned rotational behaviour in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. Brain Res. 365: 379–382

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Our experiments in this field are supported by grants from the UK Medical Research Council, Parkinson’s UK, and the European Union Seventh Framework programme.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stephen B. Dunnett .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Dunnett, S.B., Torres, E.M. (2011). Rotation in the 6-OHDA-Lesioned Rat. 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_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-298-4_15

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-297-7

  • Online ISBN: 978-1-61779-298-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics