Neurotoxicity Research

, Volume 4, Issue 1, pp 41–49 | Cite as

Time course of deficits in open field behavior after unilateral neostriatal 6-hydroxydopamine lesions

  • Jaime Fornaguera
  • Rainer K. W. SchwartingEmail author


In this study, the degree and time course of deficits in open field behavior was analyzed in male Wistar rats (aged 1 year) which had received unilateral neostriatal lesions with 6-OHDA. The post-mortem neurochemical analysis showed that dopamine was partly depleted in the lateral (to 45%), and in the medial neostriatum (65%). In spontaneous (i.e. undrugged) open field behavior, lesion-dependent asymmetries were observed in turning and scanning. The time courses of asymmetry differed between the two measures, since pronounced ipsiversive asymmetries in turning were observed within the first days after lesion placement and persisted throughout the postoperative testing period of 30 days, whereas the ipsilateral asymmetry in scanning appeared during the first week and remained stable thereafter. Systemic treatment with the dopamine receptor agonist apomorphine reversed the asymmetry in turning, indicating supersensitivity of postsynaptic neostriatal dopamine receptors. Furthermore, an enhanced grooming response to apomorphine was measured; however, only in those animals with the more severe 6-OHDA lesions. These findings are discussed in comparison to those obtained with 6-OHDA lesions placed at the level of dopamine cell bodies or fibers, the role of neostriatal dopamine depletion, and the possible relationships with progressive neurodegeneration.


Turning Thigmotactic scanning Locomotion 6-Hydroxydopamine Dopamine Apomorphine Parkinson's disease Recovery 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Altar, C.A., Jakeman, L.B., Acworth, I.N., Soriano, R. and Dugich-Djordjevic, M. (1992) “Regionally restricted loss and partial recovery of nigrostriatal dopamine input following intrastriatal 6-hydroxydopamine”,Neurodegeneration 1, 123–133.Google Scholar
  2. Antoniou, K., Papadopoulo-Daifotis, Z. and Kafetzopoulos, E. (1998) “Differential alterations in basal andd-amphetmaineinduced behavioural pattern following 6-OHDA or ibotenic acid lesions into the dorsal striatum”,Behav. Brain Res. 97, 13–28.PubMedCrossRefGoogle Scholar
  3. Barnéoud, P., Descombris, E., Aubin, N. and Abrous, D.N. (2000) “Evaluation of simple and complex sensorimotor behaviours in rats with a partial lesion of the dopaminergic nigrostriatal system”,Eur. J. Neuroscience 12, 322–336.CrossRefGoogle Scholar
  4. Berridge, K.C. (1989) “Substantia nigra 6-OHDA lesions mimic striatopallidal disruption of synaptic grooming chains: a neural systems analysis of sequence control”,Psychobiology 17, 377–385.Google Scholar
  5. Cadet, J.L., Katz, M., Jackson-Lewis, V. and Fahn, S. (1989) “Vitamin E attenuates the toxic effects of intrastriatal injection of 6-hydroxydopamine (6-OHDA) in rats: behavioral and biochemical evidence”,Brain Res. 476, 10–15.PubMedCrossRefGoogle Scholar
  6. Cadet, J.L., Last, R., Kostic, V., Przedborski, S. and Jackson-Lewis, V. (1991) “Long-term behavioral and biochemical effects of 6-hydroxydopamine injections in rat caudate-putamen”,Brain Res. Bull. 26, 707–713.PubMedCrossRefGoogle Scholar
  7. Chang, J-W., Wachtel, S.R., Young, D. and Kang, U-J. (1999) “Biochemical and anatomical characterization of forepaw adjusting steps in rat models of Parkinson's disease: studies on medial forebrain bundle and striatal lesions”,Neuroscience 88, 617–628.PubMedCrossRefGoogle Scholar
  8. Choi-Lundberg, D.L., Lin, Q., Schallert, T., Crippens, D., Davidson, B.L., Chang, Y-N., Chiang, Y.L., Qian, J., Bardwa, L. and Bohn, M.C. (1998) “Behavioral and cellular protection of rat dopaminergic neurons by an adenoviral vector encoding glial cell line-derived neurotrophic factor”,Exp. Neurol. 154, 261–275.PubMedCrossRefGoogle Scholar
  9. Cutillas, B., Espejo, M., Gil, J., Ferrer, I. and Ambrosio, S. (1999) “Caspase inhibition protects nigral neurons against 6-OHDA-induced retrograde degeneration”,Neuro Report 10, 2605–2608.Google Scholar
  10. Dunnett, S.B. and Iversen, S.D. (1982a) “Spontaneous and drug-induced rotation following localized 6-hydroxydopamine and kainic acid-induced lesions of the neostriatum”,Neuropharmacology 21, 899–908.PubMedCrossRefGoogle Scholar
  11. Dunnett, S.B. and Iversen, S.D. (1982b) “Sensorimotor impairments following localized kainic acid and 6-hydroxydopamine lesions of the neostriatum”,Brain Res. 248, 121–127.PubMedCrossRefGoogle Scholar
  12. Fornaguera, J. and Schwarting, R.K.W. (1999) “Early behavioral changes after nigro-striatal system damage can serve as predictors of striatal dopamine depletion”,Prog. Neuro-Psychopharmacol. Biol. Psychiat. 23, 1353–1368.CrossRefGoogle Scholar
  13. Fornaguera, J., Schwarting, R.K.W., Boix, F. and Huston, J.P. (1993) “Behavioral indices of moderate nigro-striatal 6-hydroxydopamine lesion: a preclinical Parkinson's model”,Synapse 13, 179–185.PubMedCrossRefGoogle Scholar
  14. Fornaguera, J., Carey, R.J., Huston, J.P. and Schwarting, R.K.W. (1994a) “Behavioral asymmetries and recovery in rats with different degrees of unilateral striatal dopamine depletion”,Brain Res. 664, 178–188.PubMedCrossRefGoogle Scholar
  15. Fornaguera, J., Carey, R.J., Dai, H., Huston, J.P. and Schwarting, R.K.W. (1994b) “Differentiation of motor inactivation from asymmetry effects in an animal model of hemi-Parkinsonism”,Neuro Report 6, 173–176.Google Scholar
  16. Kirik, D., Rosenblad, C. and Björklund, A. (1998) “Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat”,Exp. Neurol. 152, 259–277.PubMedCrossRefGoogle Scholar
  17. Lee, C.S., Sauer, H. and Björklund, A. (1996) “Dopaminergic neuronal degeneration and motor impairments following axon terminal lesion by intrastriatal 6-hydroxydopamine in the rat”,Neuroscience 72, 641–653.PubMedCrossRefGoogle Scholar
  18. Lindner, M.D., Cain, C.K., Plone, M.A., Frydel, B.R., Blaney, T.J., Emerich, D.F. and Hoane, M.R. (1999) “Incomplete nigrostriatal dopaminergic cell loss and partial reductions in striatal dopamine produced akinesia, rigidity, tremor and cognitive deficits in middle-aged rats”,Behav. Brain Res. 102, 1–16.PubMedCrossRefGoogle Scholar
  19. Murrin, L.C., Gale, K. and Kuhar, M.J. (1979) “Autoradiographic localization of neuroleptic and dopamine receptors in the caudate-putamen and substantia nigra: effects of lesions”,Eur. J. Pharmacol. 60, 229–235.PubMedCrossRefGoogle Scholar
  20. Paxinos, G. and Watson, C. (1986) The Rat Brain in Stereotaxic Coordinates (Academic Press, San Diego).Google Scholar
  21. Przedborksi, S., Levivier, M., Jiang, H., Ferreira, M., Jackson-Lewis, V., Donaldson, D. and Togasaki, D.M. (1995) “Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by intrastriatal injection of 6-hydroxydopamine”,Neuroscience 67, 631–647.CrossRefGoogle Scholar
  22. Reading, P.J. and Dunnett, S.B. (1994) “6-Hydroxydopamine lesions of nigrostriatal neurons as an animal model of Parkinson's disease”, In: Woodruff, M.L. and Nonneman, A.J., eds, Toxin-induced Models of Neurological Disorders (Plenum Press, New York), pp 89–119.Google Scholar
  23. Rosenblad, C., Martinez, A. and Björklund, A. (1998) “Intrastriatal glial cell line-derived neurotrophic factor promotes sprouting of spared nigrostriatal dopaminergic afferents and induces recovery of function in a rat model of Parkinson's disease”,Neuroscience 82, 129–137.PubMedCrossRefGoogle Scholar
  24. Sauer, H. and Oertel, W.H. (1994) “Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde tracing and immunocytochemical study in the rat”,Neuroscience 59, 401–415.PubMedCrossRefGoogle Scholar
  25. Sautter, J., Kupsch, A., Earl, C.D. and Oertel, W.H. (1997) “Degeneration of pre-labelled nigral neurons induced by intrastriatal 6-hydroxydopamine in the rat: behavioural and biochemical changes and pretreatment with the calcium-entry blocker nimodipine”,Exp. Brain Res. 117, 111–119.PubMedCrossRefGoogle Scholar
  26. Schwarting, R.K.W. and Huston, J.P. (1987) “Dopamine and serotonin metabolism in brain sites ipsi- and contralateral to direction of conditioned turning in rats”,J. Neurochem 48, 1473–1479.PubMedCrossRefGoogle Scholar
  27. Schwarting, R.K.W. and Huston, J.P. (1996a) “Unilateral 6-hydroxydopamine lesions of meso-striatal dopamine neurons and their physiological sequelae”,Prog. Neurobiol. 49, 215–266.PubMedCrossRefGoogle Scholar
  28. Schwarting, R.K.W. and Huston, J.P. (1996b) “The unilateral 6-hydroxydopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery and treatments”,Prog. Neurobiol. 50, 275–331.PubMedCrossRefGoogle Scholar
  29. Schwarting, R.K.W., Bonatz, A.E., Carey, R. and Huston, J.P. (1991) “Relationships between indices of behavioral asymmetries and neurochemical changes following mesencephalic 6-hydroxydopamine injections”,Brain Res. 554, 46–55.PubMedCrossRefGoogle Scholar
  30. Schwarting, R.K.W., Fornaguera, J. and Huston, J.P. (1995) “Automated video-image analysis of behavioral asymmetries”, In: Sanberg, P.R., Ossenkopp, K.P. and Kavaliers, M., eds, Motor Activity and Movement Disorders (Humana Press Inc Totowa, NJ)141–174, pp 141–174.Google Scholar
  31. Sundström, E., Henriksson, B.G., Mohammed, A.H. and Souverbie, F. (1994) “MPTP-treated mice: a useful model for parkinson's disease”, In: Woodruff, M.L. and Nonneman, A.J., eds, Toxin-induced Models of Neurological Disorders (Plenum Press, New York), pp 121–137.Google Scholar
  32. Ungerstedt, U. (1976) “6-Hydroxydopamine-induced degeneration of the nigro-striatal dopamine pathway: the turning syndrome”,Pharmac. Ther. 2, 37–40.Google Scholar
  33. Zigmond, M.J. (1997) “Do compensatory processes underlie the preclinical phase of neurodegenerative disease? Insights from animal models of Parkinsonism”,Neurobiol. Dis. 4, 247–253.PubMedCrossRefGoogle Scholar

Copyright information

© Taylor & Francis Ltd 2002

Authors and Affiliations

  1. 1.Department of Biochemistry, School of MedicineUniversity of Costa RicaCosta Rica
  2. 2.Institute of Experimental and Physiological PsychologyPhilipps-University of MarburgMarburgGermany

Personalised recommendations