Effects of complete and partial lesions of the dopaminergic mesotelencephalic system on skilled forelimb use in the rat

This study compares certain behavioural consequences of partial and complete unilateral lesions of the dopaminergic mesotelencephalic system. We investigated skilled forelimb use, rotations induced by apomorphine and amphetamine, and dopaminergic metabolism of the nigrostriatal system of rats that h...

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Bibliographic Details
Published in:Neuroscience 1995, Vol.67 (4), p.837-848
Main Authors: Barnéoud, P., Parmentier, S., Mazadier, M., Miquet, J.M., Boireau, A., Dubédat, P., Blanchard, J.-C.
Format: Article
Language:English
Subjects:
Animals
Apomorphine - pharmacology
Behavior, Animal
Biological and medical sciences
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Disease Models, Animal
Dopamine - metabolism
Forelimb - physiology
Medical sciences
Neurology
Parkinson Disease
Rats
Rats, Inbred Strains
Rotation
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Summary:This study compares certain behavioural consequences of partial and complete unilateral lesions of the dopaminergic mesotelencephalic system. We investigated skilled forelimb use, rotations induced by apomorphine and amphetamine, and dopaminergic metabolism of the nigrostriatal system of rats that had received a unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. The rats classified Apo(+), that rotated after the administrations of apomorphine, had a complete lesion of the nigrostriatal system, whereas those classified Apo(−), that did not rotate after the administration of apomorphine, had a partial lesion of the nigrostriatal system. In the Apo(+) rats, 99.8% of the dopamine in the striatum was depleted, as was 85% of that in the substantia nigra. For the Apo(−) rats, 72% of the dopamine in the striatum was depleted as was 56% of that in the substantia nigra. When investigated with the staircase test, the animals with the most severe dopamine depletions were those most impaired in the paw reaching task. Complete and partial unilateral depletions of the dopaminergic mesotelencephalic system impaired the heirarhic phases of paw reaching differently. A complete dopamine depletion, but not a partial one, decreased the number of attempts made with the contralateral paw, and induced a bias towards the ipsilateral paw. A partial dopamine lesion impaired the sensorimotor co-ordination of both paws, whereas the complete dopamine lesion had a greater effect on the contralateral paw than on the ipsilateral paw. The mild paw reaching impairments observed in animals with moderate depletions of dopamine are proposed as a model of the early symptoms of Parkinson's disease that may be useful for the development of protective or restorative therapies.
ISSN:0306-4522
1873-7544
DOI:10.1016/0306-4522(95)00112-V