The effect of GDNF on nigrostriatal dopaminergic function in response to atwo-pulse K+ stimulation

We examined the effect of glial cell line-derived neurotrophic factor (GDNF ) upon nigrostriatal dopaminergic function in response to two-pulse potassi um (K+) stimulation in rats under in vivo microdialysis conditions. The two -pulse infusion protocol permits us to focus upon the role of this neurotro phin as related to vesicular storage and release of dopamine (DA). The effe cts 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 ipsi lateral intrastriatal injection of vehicle, 1 mug GDNF, or 10 mug GDNF 1 we ek before microdialysis were examined. In the 10 mug GDNF-treated rats, the re was a significant increase in the peak DA output in response to the seco nd versus first K+ infusion, a significant increase in both basal and overa ll K+-evoked DOPAC responses, and significantly increased striatal DA and D OPAC contents compared with vehicle- or 1 mug GDNF-treated rats. These data demonstrate that two-pulse K+ stimulation is a useful means to detect sign ificant mechanistic changes in DA neurons resulting from GDNF treatment. Th ese results suggest the possibility for GDNF to modulate vesicular pools of DA for release. (C) 2000 Academic Press.