GABA-B Receptors and Parkinson’s Disease

Smith, Yoland, Ph.D.
Emory University, Atlanta, GA

Abstract

Preliminary studies at Emory University have shown that GABA (a neurotransmitter) subtypes are involved in reducing gultamte release from subthalamic nucleus (STN) terminals in the globus pallidum (Gpi). Overactivity from the STN to Gpi, decreased when the activity of the STN is controlled by deep-brain stimulation, may also be able to be controlled pharmaceutically. Drs. Yoland Smith, Thomas Wichmann and J. Timothy Greenamyre now will test GABA receptor agonists in not-human primates as putatively useful antiparkinson drugs. Their studies should also continue to elucidate the functional anatomy of the overall brain area involved in PD, the basal ganglia, a major interest of Dr. Greenamyre since his early work with Drs. Anne Young and John Penney, considered the architects” of the anatomic description of the basal ganglia.

Progress Report (as of 8/2002)

Gamma-aminobutyric acid (GABA) is the main inhibitory (as opposed to excitatory) neurotransmitter in the brain and there are two major subtypes of GABA receptors, A and B. GABA-B receptors appear on the glutamatergic axon terminals in the brain area called the globus pallidus, one involved in PD. Since it is thought that glutamate may be harmful, either causing or exacerbating PD symptoms, reducing glutamate by increasing GABA might ease PD symptoms. (This group, Drs. Yoland Smith, Thomas Wichmann and J. Timothy Greenamyre at Emory University in Atlanta, is also looking at glutamate antagonists, aiming for the same effects from the other side, so to speak.) Baclofen is a potent GABA-B receptor agonist and, when administered in low dosage along with a similarly low dosage of levodopa, significantly improved the rigidity and akinesia of MPTP monkey models of parkinsonism. This new research avenue will continue under a major grant newly acquired from NIH.