PHENOTYPIC PLASTICITY OF GRAFTED CATECHOLAMINERGIC CELLS IN THE DOPAMINE-DEPLETED CAUDATE-NUCLEUS IN THE RAT

Catecholamine-producing cells were grafted in the caudate nucleus of model rats with hemi-Parkinson's disease - animals with unilateral 6-hydroxydopamine (6-OHDA) lesions in the nigrostriatal dopaminergic pathway. Survival of the grafted cells, dopamine synthesis/release, and recovery from motor imbalance were investigated. Motor imbalance (methamphetamine rotations) recovered in more than 90% of animals by grafting of nigral dopaminergic (DAergic) cells, in 40-60% of animals by grafting of locus coeruleus noradrenergic (LC-NAergic) cells, and in 0-30% of animals by grafting of adrenal medullary cells. Many tyrosine hydroxylase (TH)-positive cells survived in the host caudate after grafting of DAergic cells. A moderate number of TH-positive but dopamine-β-hydroxylase (DBH)-negative cells survived after grafting of NAergic cells. A few TH-positive neuron-like cells survived after grafting of adrenal medullary cells. In vivo microdialysis revealed that extracellular DA recovered up to 50-80% of that of control level, and dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) up to 25-50% of those of controls in animals that showed motor recovery after grafting. Using a TH cDNA probe, TH-positive cells were found to express TH mRNA in an in-situ hybridization-autoradiographic study. Animals that received 6-OHDA lesion only or animals that received grafting but had no surviving cells showed neither behavioral nor chemical recovery. The data suggest that grafted catecholaminergic cells survive, make phenotypic plasticity, synthesize/release dopamine, and ameliorate motor function. © 1990.