GDNF protects against 6-OHDA nigrostriatal lesion: In vivo study with microdialysis and PET

WE have investigated whether glial cell line-derived neurotrophic factor (GDNF) protects against a complete unilateral 6-hydroxydopamine (6-OHDA) nigrostriatal lesion, a robust rat model of Parkinson's disease. GDNF or vehicle were administered above the rat substantia nigra and into the lateral ventricle immediately before an ipsilateral 6-OHDA injection into the medial forebrain bundle. In vivo tests were employed to assess the effects of the treatment: microdialysis to measure striatal dopamine release, amphetamine challenge to estimate turning behaviour, and positron emission tomography (PET) to image dopamine reuptake sites. The present results show that GDNF can protect dopaminergic neurones against an acute and irreversible 6-OHDA lesion. They are encouraging for potential use of GDNF in Parkinson's disease.