Dynamic regulation of striatal dopaminergic grafts during locomotor activity

Abstract

The present experiment was designed to estimate the neurochemical activity of dopaminergic grafts in hemiparkinsonian model rats during locomotion and to examine the functional importance of dynamic regulation of the grafted neurons in the host brain. Rats were trained to run on a straight treadmill at various speeds (300, 660, 1200, 1800 cm/min), and extracellular dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were measured by in vivo microdialysis during and after running. Grafted rats were divided into two groups depending on their running ability and data were compared with those of normal and lesioned controls. Although the tonic level of extracellular DA in grafted rats recovered to 70% of control, levels of DOPAC and HVA remained 15–20% of controls. A small number of grafted rats showed full recovery in treadmill running tasks. In these animals, the percentage increase in DOPAC and HVA showed similar time courses and magnitudes as those in normal rats. Most grafted rats showed partial recovery in locomotor ability. The percentage increase in DOPAC and HVA in these animals remained at a lower level than that in normal rats, though the tonic levels of DA, DOPAC and HVA were not lower than those of fully recovered rats. Data suggest that grafted DAergic cells in functionally well recovered rats were dynamically regulated in the host brain in an actual behavior and that well-controlled release of DA might be involved in the recovery of complex motor behavior, such as high speed locomotion.