Effects of intra-striatal GDNF on motor coordination and striatal electrophysiology in aged F344 rats

The purpose of this study was to examine whether improvement in motor funct ion could be demonstrated in old rats, and to see if GDNF affected post-syn aptic DA function. Aged (20 month old) versus young rats were tested follow ing GDNF treatment for postural control by using an inclined balance beam a nd a wire grip strength test. Rats were also examined electrophysiologicall y for spontaneous striatal cell firing rate alone and in the presence of DA receptor agonists, and histologically for the intensity of striatal TH sta ining, and number of DA containing nigral cells. Behavior was significantly improved in the aged animals who received central GDNF infusions, although the extent of improvement was less than what has been observed in 16-month -old rats. There was no effect of GDNF treatment in the aged animals on spo ntaneous firing rate in the striatum, or on the post synaptic response to l ocally applied D-1 and D-2 receptor family agonists. However, there was an effect of age alone on firing rare, and on the response to locally applied SKF 38393 and quinpirole. By using unbiased cell counting we observed no ag e-related decline in the number of TH positive cells in the substantia nigr a. There was no effect of GDNF on the number of TH positive cells in the su bstantia nigra in either young or aged rats, although there were morphologi cal improvements in DA neurons of the GDNF treated aged rats. These results replicate earlier studies showing an effect of age on striatal firing rate and dopamine receptor function, and suggest that the GDNF mediated improve ment in behavior may be located other than post synaptically within the str iatum. (C) 2000 Published by Elsevier Science Inc. All rights reserved.