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.