Abstract
Lesions of the dopaminergic nigrostriatal tract produce a range of motor and sensorimotor deficits. One of the simplest and most reliable is the rotational response of the animal following activation with drugs that stimulate the dopaminergic network, most notably amphetamine and apomorphine. Consequently, the rotation test has been extensively used in assessing the success of treatments designed to restore dopaminergic function, including neural transplants. The present study investigates whether rotation induced by 6-hydroxydopamine lesions of the nigrostriatal bundle in rats is modified by additional lesions in the neostriatum. It was found that apomorphine-induced rotation can be reduced by ibotenic acid lesions of the dopamine-deafferented striatum, and that the extent of the reduction was proportional to the size of the lesions. In contrast, such lesions produced a non-significant reduction in amphetamine-induced rotation, although the correlation between the extent of the reduction and the size of the lesion was again apparent. Since the pattern of change was similar in direction, albeit smaller in magnitude, than the previously reported effects of intrastriatal transplantation in rats with similar nigrostriatal lesions, rotation tests alone do not provide an unequivocal test of graft survival and function.
Similar content being viewed by others
References
Barker RA, Dunnett SB (1992) Grafts of adrenal medulla and/or adrenal cortex differentially affect apomorphine and amphetamine induced rotation in the 6-OHDA-lesioned rat. Restor. Neurol Neurosci 4:158
Barker RA, Dunnett SB (1993) The biology and behaviour of intracerebral adrenal transplants in animal and man. Rev Neurosci 4:113–146
Bing G, Notter MFD, Hansen JT, Gash DM (1988) Comparison of adrenal medullary, carotid body and PC12 cell grafts in 6OHDA lesioned rats. Brain Res Bull 20:399–406
Björklund A, Lindvall O (1986) Catecholaminergic brain stem regulatory systems. In Handbook of physiology: Sect 1 — The nervous system, vol 4 — Intrinsic regulatory systems of the brain. American Physiological Society, pp 155–236
Björklund A, Lindvall O, Isacson O, Brundin P, Wictorin K, Srecker RE, Clarke DJ, Dunnett SB (1987) Mechanisms of action of intracerebral neural implants: studies on nigral and striatal grafts to the lesioned striatum. Trends Neurosci 10:509–516
Bohn MC, Cupit L, Marciano F, Gash DM (1987) Adrenal medulla grafts enhance recovery of striatal dopaminergic fibres. Science 237:913–916
Brown VJ, Dunnett SB (1989) Comparison of adrenal and fetal nigral grafts on drug induced rotation in rats with 6OHDA lesions. Exp Brain Res 78:714–718
Cenci MA, Björklund A (1993) Transection of corticostriatal af ferents reduces amphetamine and apomorphine-induced striatal fos expression and turning behaviour in unilaterally 6-hydroxydopamine-lesioned rats. Eur J Neurosci 5:1062–1070
Clough CG (1991) Parkinson's disease: management. Lancet 337:1324–1327
Dunnett SB (1991) Transplantation of embryonic dopamine neurons: what we know from rats. J Neurol 238:65–74
Dunnett SB, Björklund A, Stenevi U, Iversen SD (1981) Grafts of embryonic substantia nigra reinnervating the ventrolateral striatum ameliorate sensorimotor impairments and akinesia in rats with 6-OHDA lesions of the nigrostriatal pathway. Brain Res 229:209–217
Dunnett SB, Hernandez TD, Summerfield A, Jones GH, Arbuthnott G (1988a) Graft derived recovery from 6-OHDA lesions: specificity of ventral mesencephalic tissue. Exp Brain Res 71:411–424
Dunnett SB, Isacson O, Sirinathsinghji DJS, Clarke DJ, Björklund A (1988b) Striatal grafts in rats with unilateral neostriatal lesions: recovery from dopamine dependent asymetry and deficits in skilled paw reaching. Neurosci 24:813–820
Emerich DF, Ragozzino M, Lehman MN, Sanberg PR (1992) Behavioral effects of neural transplantation. Cell Transpl 1:401–427
Ewing SE, Weber RJ, Zauner A, Plunkett RJ (1992) Recovery in hemiparkinsonian rats following intrastriatal implantation of activated leukocytes. Brain Res 576:42–48
Fisher LJ, Jinnah HA, Kale LC, Higgins GA, Gage FH (1991) Survival and function of intrastriatally grafted primary fibroblasts genetically modified to produce L-Dopa. Neuron 6:371–380
Forno LS (1990) Pathology of Parkinson's disease: the importance of the substantia nigra and Lewy bodies. In: Stern GM (ed) Parkinson's disease. Chapman and Hall, London, pp 185–238
Freed WJ (1991) Substantia nigra grafts and Parkinson's disease: from animal experiments to human therapeutic trials. Restor Neurol Neurosci 3:109–134
Freed WJ, Perlow MJ, Karoum F, Seiger A, Olson L, Hoffer BJ, Wyatt RJ (1980) Restoration of dopaminergic function by grafting of fetal rat substantia nigra to the caudate nucleus: long-term behavioural, biochemical and histochemical studies. Ann Neurol 8:510–519
Freed WJ, Poltorak M, Becker JB (1990) Intracerebral adrenal medulla grafts: a review. Exp Neurol 110:139–166
Friehs GM, Parker RG, He LE, Haines SJ, Turner DA, Ebner TJ (1991) Lesioning of the striatum reverses motor asymmetry in the 6-hydroxydopamine rodent model of parkinsonism. J Neural Transpl Plast 2:141–156
Kamo H, Kim SU, McGeer PL, Shin DH (1986) Functional recovery in a rat model of Parkinson's disease following transplantation of cultured human sympathetic neurons. Brain Res 397:372–376
Kelly PH, Moore KE (1976) Mesolimbic dopaminergic neurones in the rotational model of nigrostriatal function. Nature 263:695–696
Koelle GB (1955) The histochemical identification of acetylcholinesterase in cholinergic, adrenergic and sensory organs. J Pharmacol Exp Ther 114:167–184
Koshikawa N, Mori E, Maruyama Y, Yatsushige N, Kobayashi M (1990) Role of dopamine D1 and D2 receptors in the ventral striatum in the turning behaviour of rats. Eur J Neurosci 178:233–237
Kuczenski R, Segal D (1989) Concomitant characterization of behavioral and striatal neurotransmitter response to amphetamine using in vivo microdialysis. J Neurosci 9:2051–2065
Loughlin SE, Fallon JH (1982) Mesostriatal projections from ventral tegmentum and dorsal raphe: cells project ipsilaterally or contralaterally but not bilaterally. Neurosci Lett 33:11–16
Mattingly BA, Gotsick JE (1989) Conditioning and experiential factors affecting the behavioral sensitization to apomorphine. Behav Neurosci 103:1311–1317
Meyers R (1951) Surgical experiments in the therapy of certain ‘extrapyramidal’ diseases: a current evaluation. Acta Psychiatr Neurol 67 [Suppl 13]: 1–42
Motti ED, Pezzoli G, Silani V, Scarlato G (1988) Surgical lesions, parkinsonism and brain graft operations. Lancet II:346
Narang N, Hunt ME, Pundt LL, Alburges ME, Wamsley JK (1993) Unilateral ibotenic acid lesion of the caudate putamen results in D2 receptor alterations on the contralateral side. Exp Neurol 121:40–47
Norman AB, Norgren RB, Wyatt LM, Hildebrand JP, Sanberg PR (1992) The direction of apomorphine-induced rotation behavior is dependent on the location of excitotoxin lesions in the rat basal ganglia. Brain Res 569:169–172
Pasinetti GM, Morgan DG, Finch CE (1991) Disappearance of GAD-mRNA and tyrosine hydroxylase in substantia nigra following striatal ibotenic acid lesions. Exp Neurol 112:131–139
Paul ML, Graybiel AM, David J-C, Robertson HA (1992) D1-like and D2-like dopamine receptors synergistically activate rotation and c-fos expression in the dopamine-depleted striatum in a rat model of Parkinson's disease. J Neurosci 12:3729–3742
Pezzoli G, Fahn S, Dwork A, Truong DD, de Yebenes JG, Jackson-Lewis V, Herbert J, Cadet JL (1988) Non-chromaffin tissue plus nerve growth factor reduces experimental parkinsonism in aged rats. Brain Res 459:398–403
Plunkett RJ, Bankiewicz KS, Cummins AC, Miletich RS, Schwartz JP, Oldfield EH (1990) Long-term evaluation of hemiparkinsonian monkeys after adrenal autografting or cavitation alone. J Neurosurg 73:918–926
Pycock CJ (1980) Turning behaviour in animals. Neuroscience 5:461–514
Pycock CJ, Marsden CD (1978) The rotating rodent: a two-component system. Eur J Pharmac 47:167–175
Reading PJ (1992) The ventral striatum: function and repair. PhD Thesis, University of Cambridge
Riopelle RJ (1988) Adrenal medulla autografts in Parkinson's disease: a proposed mechanism of action. Can J Neurol Sci 15:366–370
Rowlett JK, Mattingly BA, Bardo MT (1993) Neurochemical correlates of behavioral sensitization following repeated apomorphine treatment: assessment of the role of D1 dopamine receptor stimulation. Synapse 14:160–168
Sanberg PR, Henault MA, Deckel AW (1986) Locomotor hyperactivity: effects of multiple striatal transplants in an animal model of Parkinson's disease. Pharmacol Biochem Behav 25:297–300
Schwartz R, Kuxe K, Agnati LF, Hökfelt T, Coyle JT (1979) Rotational behaviour in rats with unilateral striatal kainic acid lesions: a behavioural model for studies on intact dopamine receptors. Brain Res 170:485–495
Surmeier DJ, Eberwine J, Wilson CJ, Cao Y, Stefani A, Kitai ST (1992) Dopamine receptor subtypes colocalize in rat striatonigral neurons. Proc Natl Acad Sci 89:10178–10182
Takashima H, Walker BR, Cannon-Spoor HE, Freed WJ (1993) Kainic acid lesions increase reafferentation of the striatum by substantia nigra grafts. Brain Res 621:71–78
Ungerstedt U (1971a) Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behavior. Acta Physiol Scand 82 [Suppl 367]:49–68
Ungerstedt U (1971b) Postsynaptic supersensitivity after 6-hydroxydopamine-induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand 82 [Suppl. 367]:69–93
Ungerstedt U, Arbuthnott G (1970) Quantitative recording of rotational behaviour in rats with 6-hydroxy-dopamine lesions of the nigro-striatal dopamine systems. Brain Res 24:485–493
Williams JA (1991) Mechanisms of hormone secretion and action. In: Greenspan FS (ed) Basic and clinical endocrinology, 3rd ed Prentice Hall, London, pp 1–19
Winn SR, Wahlberg L, Tresco PA, Aebischer P (1989) An encapsulated dopamine releasing polymer alleviates experimental parkinsonism in rats. Exp Neurol 105:244–250
Wolf ME, White FJ, Nassar R, Brooderson RJ, Khansa MR (1993) Differential development of autoreceptor subsensitivity and enhanced dopamine release during amphetamine sensitization. J Pharm Exp Therap 264:249–255
Zetterström T, Brundin P, Gage FH, Sharp T, Isacson O, Dunnett SB, Ungerstedt U, Björklund A (1986) In vivo measurement of spontaneous release and metabolism of dopamine from intrastriatal nigral grafts using intracerebral dialysis. Brain Res 362:344–349
Zigmond MJ, Stricker EM (1989) Animal models of parkinsonism using selective neurotoxins: clinical and basic implications. Int Rev Neurobiol 31:1–79
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Barker, R., Dunnett, S.B. Ibotenic acid lesions of the striatum reduce drug-induced rotation in the 6-hydroxydopamine-lesioned rat. Exp Brain Res 101, 365–374 (1994). https://doi.org/10.1007/BF00227330
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00227330