Functional effects of GDNF in normal rat striatum: presynaptic studies using in vivo electrochemistry and microdialysis.
The functional effects of a single dual-site intranigral administration (10 micrograms) of glial cell line-derived neurotrophic factor (GDNF) on dopamine (DA) neurons in the basal ganglia of young Fischer 344 rats were investigated. A combination of behavioral, in vivo electrochemical, microdialysis and high-performance liquid chromatography methods were used to study the effects of this novel peptide. Behaviorally, significant changes in spontaneous locomotor activity were found 1 week, but not 3 weeks, after GDNF treatment. However, the velocity of movements was increased in the GDNF-treated animals 3 weeks after GDNF administration, a result that corresponded to significant enhancement of stimulus-evoked release of DA. Two-fold increases in potassium-evoked DA overflow were seen throughout the striatum by means of high-speed chronoamperometry 3 weeks after GDNF injection. No significant change in basal levels of DA was measured by microdialysis, although both potassium-evoked and d-amphetamine-induced DA overflow were significantly increased 3 weeks after treatment. Finally, significant changes in whole-tissue levels of DA were seen in the substantia nigra 1 week, but not 3 weeks, after GDNF administration. These data represent the first studies demonstrating that GDNF has long-lasting functional presynaptic effects on DA-containing neurons in the rat striatum.
Hebert
M A
MA
Neuroscience Training Program, University of Colorado Health Sciences Center Denver, USA.
Van Horne
C G
CG
Hoffer
B J
BJ
Gerhardt
G A
GA
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004563:Electrochemistry; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000378:metabolism
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D004298:Dopamine