This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.During the reporting period, we investigated the effects of dopamine on neuronal activity and the distribution of dopamine receptors in the substantia nigra pars reticulata in normal and parkinsonian monkeys. Parkinsonism is produced by treatment with the dopaminergic neurotoxin MPTP. We completed our work on the effects of dopamine D1-like receptor (D1LR) agonists on the electrophysiologic activity of neurons in the substantia nigra pars reticulata (SNr) in MPTP-treated monkeys. This has now been studied in three animals. We found that D1LR agonists strongly inhibit SNr activity, and that they increase neuronal bursting and oscillatory activity in this nucleus. We have also begun to study the activity of D2-like receptor (D2LR) agonists and antagonists on SNr activity. Thus far, the experiments have been completed in one animal, but the data arer not yet analyzed. We have also prepared a second animal for these studies, and plan to study D2LR actions in at least one MPTP-treated animal in the next year. Finally, we have completed our electron microscopic studies on the distribution of D1LRs in the SNr, using material from seven normal and five MPTP-treated animals. These studies showed that D1LRs are located primarily in unmyelinated axons, but that a subtype of these receptors (D5-receptors) is also found postsynaptically. There were no significant differences between normal and parkinsonian animals. These studies provided insights into the anatomic basis and functional effects of nigral dopamine release in monkeys in the normal state and in parkinsonism. We have shown that functional D1LRs are present in the primate SNr, suggesting that therapies aimed at these receptors may have antiparkinsonian properties
Showing the most recent 10 out of 912 publications
