BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF INTRANIGRAL ADMINISTRATION OFGLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR ON AGED FISCHER-344 RATS

To investigate the efficacy of glial cell line-derived neurotrophic fa ctor (GDNF) in the augmentation of functional dopaminergic (DAergic) i ndices in aged rats, 24-month-old Fischer 344 (F344) rats received sin gle intranigral injections of 10 mu g GDNF (in 10 mu l phosphate-buffe red saline) or 10 mu l phosphate-buffered saline. In locomotor activit y tests, the GDNF-treated animals exhibited significant increases in b oth total distance traveled and movement speed compared with the vehic le group, 3 weeks after injections. In vivo microdialysis studies show ed that basal extracellular levels of dopamine (DA) and its metabolite s, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were signific antly increased in the striatum of the GDNF-treated rats. In addition, both potassium-(100 mM, K+) and d-amphetamine (250 mu M)-induced DA o verflow were augmented in the striatum and nucleus accumbens of the ag ed rats injected with GDNF, Whole-tissue levels of DA and DA metabolit es, as measured by high-performance liquid chromatography coupled with electrochemical detection, in the nucleus accumbens and substantia ni gra were also elevated after GDNF administration, These results indica te that a single intranigral injection of GDNF is capable of augmentin g locomotor behavior and DAergic function in the aged rat striatum and nucleus accumbens. This is the first report to demonstrate that a sin gle intranigral injection of GDNF Can improve the functional capacity of DAergic neurons of aged F344 rats.