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 co mplete unilateral lesions of the dopaminergic mesotelencephalic system . We investigated skilled forelimb use, rotations induced by apomorphi ne and amphetamine, and dopaminergic metabolism of the nigrostriatal s ystem of rats that had received a unilateral injection of 6-hydroxydop amine into the medial forebrain bundle. The rats classified Apo(+), th at rotated after the administration of apomorphine, had a complete les ion 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 subst antia nigra. For the Apo(-) rats, 72% of the dopamine in the striatum was depleted as was 56% of that in the substantia nigra. When investig ated with the staircase test, the animals with the most severe dopamin e depletions were those most impaired in the paw reaching task. Comple te and partial unilateral depletions of the dopaminergic mesotelenceph alic system impaired the hierarchic 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 s ensorimotor co-ordination of both paws, whereas the complete dopamine lesion had a greater effect on the contralateral paw than on the ipsil ateral 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.