Effects of Intermittent vs Coninuous L-DOPA on GABAergic Neurons of the Basal Ganglia

Jean-Jacques, Ph.D.
Boston University School of Medicene, Boston, MA

Abstract

At Boston University, Dr. Jean-Jacques Soghomonian’s study will investigate the effects of long-term intermittent vs continuous administrations of Sinemet to parkinsonian rats in an attempt to better understand how each method affects other neurotransmitter systems. His hypothesis is that sensitization of the GABAergic system plays a role in the onset and continuation of fluctuations as well as changing the expressions of genes that effect increases or decreases of activity in the striatonigral pathway. This pathway from the striatum to the substania nigra is, as we long ago learned, the pathway that is affectd by PD and several of those parkinsonism-plus disorders that are often mistaken for PD.

Progress Report (as of 8/2002)

There are specific genes known to play roles in communications between neurons. Intermittent dosing with levodopa induces abnormalities of these genes in the striatum; continuous administration of the drug does not. In the globus pallidus, both methods of dosing prevents such abnormal expression. Seeking to determine the optimal dosage method, Dr. Jean-Jacques Soghomonian (Boston University) has used his funds to learn, in parkinsonian rats, to learn if other brain areas could also be involved in the benefits derived from levodopa. Due to his early results, he and his colleagues have just been funded by NIH to continue these studies of the GABAergic system in disease-caused fluctuations.