The effect of GDNF on nigrostriatal dopaminergic function in response to a two-pulse K(+) stimulation.
We examined the effect of glial cell line-derived neurotrophic factor (GDNF) upon nigrostriatal dopaminergic function in response to two-pulse potassium (K(+)) stimulation in rats under in vivo microdialysis conditions. The two-pulse infusion protocol permits us to focus upon the role of this neurotrophin as related to vesicular storage and release of dopamine (DA). The effects of two 20-min infusions of K(+) (70 mM) upon DA and dihydroxyphenylacetic acid (DOPAC) output from the striatum of rats which received a single ipsilateral intrastriatal injection of vehicle, 1 microgram GDNF, or 10 microgram GDNF 1 week before microdialysis were examined. In the 10 microgram GDNF-treated rats, there was a significant increase in the peak DA output in response to the second versus first K(+) infusion, a significant increase in both basal and overall K(+)-evoked DOPAC responses, and significantly increased striatal DA and DOPAC contents compared with vehicle- or 1 microgram GDNF-treated rats. These data demonstrate that two-pulse K(+) stimulation is a useful means to detect significant mechanistic changes in DA neurons resulting from GDNF treatment. These results suggest the possibility for GDNF to modulate vesicular pools of DA for release.
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Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio, 44272, USA.
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D017551:Microdialysis; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; 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; D015102:3,4-Dihydroxyphenylacetic Acid; D011188:Potassium; D004298:Dopamine