GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR - THE LATERAL CEREBRAL VENTRICLE AS A SITE OF ADMINISTRATION FOR STIMULATION OF THE SUBSTANTIA-NIGRA DOPAMINE SYSTEM IN RATS

The direct application of recombinant human glial cell line-derived ne urotrophic factor (rhGDNF) to the deep structures of the nigrostriatum has been shown previously to augment dopamine function and inhibit lo ss of substantia nigra neurons in rodent models of Parkinson's disease . The present studies were designed to determine whether administratio n of rhGDNF into the lateral ventricle, a more clinically accessible i ntracranial target, is capable of augmenting dopamine function of the nigrostriatal pathway in normal rats, Single bolus intracerebroventric ular (i.c.v.) injections of rhGDNF increased locomotor activity and de creased food and water consumption and body weight gain in a dose-depe ndent manner. rhGDNF increased concentrations of dopamine and dopamine metabolites in the substantia nigra, ventral tegmental area and hypot halamus, but had no significant effects in the striatum, rhGDNF had no effect on striatal or substantia nigral serotonin (5-HT) and 5-hydrox yindoleacetic acid levels, but these levels were significantly increas ed in the ventral tegmental area and hypothalamus respectively. The au gmentation of the dopamine and 5-HT systems was detected 2 weeks but n ot 3 days or 6 weeks after rhGDNF administration. After a repeat injec tion of i.c.v. rhGDNF (6 weeks after the initial injection), substanti a nigral dopamine, 5-HIAA and noradrenalin levels were increased. Thes e results indicate that i.c.v. administration of rhGDNF has an influen ce on adult rat dopamine neurons. This route of administration may be useful for stimulating dopamine neurons in Parkinson's disease.