Reaction time and nigrostriatal dopamine function: the effects of age and practice

Abstract

Normal aged and Parkinsonian individuals lose the ability to initiate movements rapidly (increased reaction time) in parallel with changes in the nigrostriatal dopamine (DA) system. However, the ability of these individuals to improve their reaction time with practice has not been adequately assessed. We have developed a rodent model for human reaction time in which reaction time performance correlates highly with neurochemical measures of nigrostriatal DA integrity. In the present report, 15 young and 10 old male Sprague-Dawley rats were conditioned in a reaction time task to release a lever quickly in response to external stimuli in order to avoid a mild footshock. In order to examine the effects of practice on this reaction time task, the young animals were tested for 5 days at 3, 6 and 9 months of age and the old animals were tested for 5 days at 18, 21, and 24 months of age. From this well-practiced task, reaction time response latencies were measured and compared to measures of nigrostriatal DA function (steady-state levels of DA and its metabolites, D 2 DA receptor affinity and density). The old animals were slower in response latencies than the young animals. These age differences in response latencies, however, disappeared after several days of testing at each of the 3 test sessions, so that the old animals were not significantly slower than the young animals on days 4 and 5 of each session. As expected, the old animals showed reduced striatal D 2 DA receptor density with no age differences in DA receptor affinity. The old animals had significantly higher ratios of DA metabolities (dihydroxyphenylacetic acid and homovanillic acid; DOPAC + HVA) to DA than the young animals. Furthermore, across groups there was a significant negative correlation between striatal D 2 DA receptor numbers and response latencies. This negative correlation indicated that the animals with the faster (lower) response latencies had the higher number of striatal D 2 DA receptors. These data suggest that the plasticity of the motor system allows age-related impairments in reaction time to be overcome with extensive practice. It also appears that reaction time is related to multiple aspects of nigrostriatal DA function.