Biochemical and anatomical characterization of forepaw adjusting steps in rat models of Parkinson's disease: studies on medial forebrain bundle and striatal lesions
Section snippets
Animals
The following in vivo protocols were approved by the Institutional Animal Care and Use Committee of The University of Chicago. All efforts were made to minimize animal suffering, to reduce the number of animals used, and to utilize alternatives to in vivo techniques. Female Fischer 344 rats (n=48), weighing 150–200 g were used for the first set of experiments with MFB lesions, and female Sprague–Dawley rats (n=35), weighing 150–200 g were used for the second set of experiments with striatal
Comparison of forepaw adjusting step deficits to dopamine depletion
To examine the relationship between the degree of dopamine depletion and contralateral forehand adjusting steps, the degree of dopamine depletion was correlated with the average number of contralateral forehand adjusting steps at two weeks after the lesions. Forehand adjusting steps appeared to have an all-or-none relationship with dopamine depletion. That is, the deficit in adjusting steps appeared dramatically at a threshold of approximately 80% dopamine depletion. The eight rats with less
Discussion
This study focused on deficits of forepaw adjusting steps as simplified measure of akinesia in an animal model of PD. Thus, deficits in forepaw adjusting steps were characterized both as a function of the degree of dopamine depletion after MFB lesions and as a function of the striatal subregions involved in the movement. The present results clearly indicate that testing of forepaw adjusting steps is a simple and quantitative measure, and can be used to evaluate the potential efficacy of
Conclusions
In summary, deficits in forepaw adjusting steps provide a simple and consistent behavior phenomenologically similar to akinesia in PD. The relationship between the amount of dopamine loss and the appearance of deficits is analogous to that for parkinsonian symptoms and provides a valuable model of parkinsonian akinesia. Furthermore, the stepping model has several advantages over drug-induced rotation and other models for examining various therapeutic strategies. Although the deficit occurs
Acknowledgements
This research was supported by PHS Grant R29 NS32080, Parkinson's Disease Foundation Junior Faculty Award, United Parkinson Foundation/the H.G. and Catharine Lieneman Memorial Fund, National Parkinson Foundation, Brain Research Foundation (UJK), T32 DA07255 (SRW), and Yonsei University Faculty Research Funds (JWC). We thank Nicole Nemeth and Mildred Bahn for their expert technical assistance, and Dr Michael Cousins for his critical comments on the manuscript.
References (45)
- et al.
Effects of L-DOPA on extracellular dopamine in striatum of normal and 6-hydroxydopamine-treated rats
Brain Res.
(1990) - et al.
Preservation of dopamine release in the denervated striatum
Neurosci. Lett.
(1989) - et al.
An assessment of the validity of densitomertic measures of striatal tyrosine hydroxylase-positive fibers: relationship to apomorphine-induced rotations in 6-hydroxydopamine lesioned rats
J. Neurosci. Meth.
(1990) - et al.
Partial lesion of the substantia nigra: relation between extent of lesion and rotational behavior
Brain Res.
(1991) - et al.
Skilled motor deficits in rats induced by ventrolateral striatal dopamine depletions: behavioral and pharmacological characterization
Brain Res.
(1996) - et al.
Involvement of ventrolateral striatal dopamine in movement initiation and execution: a microdialysis and behavioral investigation
Neuroscience
(1996) - et al.
Sensorimotor impairments following localized kainic acid and 6-hydroxydopamine lesions of the neostriatum
Brain Res.
(1982) - et al.
Partial lesions of the dopaminergic nigrostriatal system in rat brain: biochemical characterization
Brain Res.
(1980) - et al.
In vivo release of DOPA and dopamine from genetically engineered cells grafted to the denervated rat striatum
Neuron
(1990) - et al.
Correlation of apomorphine- and amphetamine-induced turning with nigrostriatal dopamine content in unilateral 6-hydroxydopamine lesioned rats
Brain Res.
(1993)
Dopaminergic neuronal degeneration and motor impairments following axon terminal lesion by intrastriatal 6-OHDA in the rat
Neuroscience
Behavioural recovery of rats grafted with dopamine cells after partial striatal dopaminergic depletion in a conditioned reaction-time task
Neuroscience
A 6-hydroxydopamine-induced selective parkinsonian rat model
Brain Res.
Motor functions of the striatum in the rat: critical role of the lateral region in tongue and forelimb reaching
Neuroscience
Regionally selective roles of the rat's striatum in modality-specific discrimination learning and forelimb reacing
Behav. Brain Res.
Normalization of extracellular dopamine in striatum following recovery from a partial unilateral 6-OHDA lesion of the substantia nigra: a microdialysis study in freely moving rats
Brain Res.
Dopamine depletion in a striatal subregion disrupts performance of a skilled motor task in the rat
Brain Res.
The role of brain dopamine in response initation: effects of haloperidol and regionally specific dopamine depletions on the local rate of instrumental responding
Brain Res.
Ventrolateral striatal dopamine depletions impair feeding and food handling in rats
Pharmac. Biochem. Behav.
Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde tracing and immunocytochemical study in the rat
Neuroscience
The unilateral 6-hydroxydopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery and treatments
Prog. Neurobiol.
Dopamine and skilled limb use in the rat: more severe bilateral impairments follow substantia nigra than sensorimotor cortex 6-hydroxydopamine injection
Behav. Brain Res.
Cited by (217)
ONO-2506 Can Delay Levodopa-induced Dyskinesia in the Early Stage
2023, NeurosciencePharmacological targeting of G protein-coupled receptor heteromers
2022, Pharmacological Research
- 1
Present address: Department of Neurosurgery, Yonsei University College of Medicine, CPO BOX 8044, Seoul, Korea
- 2
Present address: Department of Psychiatry, The University of Chicago, U.S.A.