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. Copyright 2000 Academic Press.