Behavioral and neurochemical effects of intranigral administration of glial cell line-derived neurotrophic factor on aged Fischer 344 rats.
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 microg GDNF (in 10 microl phosphate-buffered saline) or 10 microl 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 microM)-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.
Hebert
M A
MA
Neuroscience Training Program, and the Rocky Mountain Center for Sensor Technology, University of Colorado Health Sciences Center Denver 80262, USA.
Gerhardt
G A
GA
D000375:Aging / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D004298:Dopamine