Vol. 282, Issue 2, 760-768, 1997

Behavioral and Neurochemical Effects of Intranigral Administration of Glial Cell Line-Derived Neurotrophic Factor on Aged Fischer 344 Rats¹

Meleik A. Hebert and Greg A. Gerhardt

Neuroscience Training Program (M.A.H., G.A.G.), Departments of Psychiatry (G.A.G.) and Pharmacology (G.A.G.), and the Rocky Mountain Center for Sensor Technology (M.A.H., G.A.G.) University of Colorado Health Sciences Center Denver, Colorado

To investigate the efficacy of glial cell line-derived neurotrophic factor (GDNF) in the augmentation of functional dopaminergic (DAergic) indices in aged rats, 24-month-old Fischer 344 (F344) rats received single intranigral injections of 10 µg GDNF (in 10 µl phosphate-buffered saline) or 10 µl phosphate-buffered saline. In locomotor activity tests, the GDNF-treated animals exhibited significant increases in both total distance traveled and movement speed compared with the vehicle group, 3 weeks after injections. In vivo microdialysis studies showed that basal extracellular levels of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were significantly increased in the striatum of the GDNF-treated rats. In addition, both potassium- (100 mM, K⁺) and d-amphetamine (250 µM)-induced DA overflow were augmented in the striatum and nucleus accumbens of the aged rats injected with GDNF. Whole-tissue levels of DA and DA metabolites, as measured by high-performance liquid chromatography coupled with electrochemical detection, in the nucleus accumbens and substantia nigra were also elevated after GDNF administration. These results indicate that a single intranigral injection of GDNF is capable of augmenting locomotor behavior and DAergic function in the aged rat striatum and nucleus accumbens. This is the first report to demonstrate that a single intranigral injection of GDNF can improve the functional capacity of DAergic neurons of aged F344 rats.