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

Article type: Research Article

Authors: Schneider, J.S. | Peacock, V.

Affiliations: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA

Abstract: The ability of a single intranigral infusion of glial cell line-derived neurotrophic factor (GDNF) to reverse deficits in skilled paw usage and sensorimotor orientation and to ameliorate apomorphine-induced rotational asymmetry in unilateral 6-hydroxydopamine-lesioned rats was examined. After lesioning, all rats developed sensory inattention on the side contralateral to the lesion, rotational asymmetry in response to apomorphine administration and significant deficits in succesfully performing a forelimb reaching task dependent upon the use of somatosensory and proprioceptive feedback. A single intranigral injection of GDNF (300 µg) made 4 wks. after the 6-OHDA lesion, 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 perfomance of the paw reaching task or in sensorimotor orienting. Post mortem analyses showed that the GDNF treatment did not cause any increase in striatal dopamine levels but did increase tyrosine hydroxylase-positive immunohistochemical staining in the substantia nigra on the side of the GDNF infusion. These results demonstrate the need for multiple behavioral measures of efficacy when evaluating treatments for parkinsonism in the unilateral 6-hydroxydopamine lesion model in the rat.

Keywords: GDNF, dopamine, sensorimotor integration, behavior, rotation, paw usage, substantia nigra

Journal: Restorative Neurology and Neuroscience, vol. 13, no. 3-4, pp. 205-212, 1998