Differential effects of GDNF treatment on rotational asymmetry, skilled forelimb use deficits and sensory neglect in unilateral 6-OHDA-lesioned rats

The ability of a single intranigral infusion of glial cell line-derived neu rotrophic factor (GDNF) to reverse deficits in skilled paw usage and sensor imotor orientation and to ameliorate apomorphine-induced rotational asymmet ry in unilateral 6-hydroxydopamine-lesioned rats was examined. After lesion ing, all rats developed sensory inattention on the side contralateral to th e lesion, rotational asymmetry in response to apomorphine administration an d significant deficits in succesfully performing a forelimb reaching task d ependent upon the use of somatosensory and proprioceptive feedback. A singl e intranigral injection of GDNF (300 mu g) made 4 wks. after the 6-OHDA les ion, significantly decreased the number of drug-induced rotations at 1 and 2 wks. after GDNF administration. At the same time however, no improvements were noted in performance of the paw reaching task or in sensorimotor orie nting. Post mortem analyses showed that the GDNF treatment did not cause an y increase in striatal dopamine levels but did increase tyrosine hydroxylas e-positive immunohistochemical staining in the substantia nigra on the side of the GDNF infusion. These results demonstrate the need for multiple beha vioral measures of efficacy when evaluating treatments for parkinsonism in the unilateral 6-hydroxydopamine lesion model in the rat.