RT Journal Article
SR Electronic
T1 Functional effects of GDNF in normal rat striatum: presynaptic studies using in vivo electrochemistry and microdialysis.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1181
OP 1190
VO 279
IS 3
A1 M A Hebert
A1 C G Van Horne
A1 B J Hoffer
A1 G A Gerhardt
YR 1996
UL http://jpet.aspetjournals.org/content/279/3/1181.abstract
AB 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.