Distribution and roles of metabotropic glutamate receptors in the basal ganglia motor circuit: implications for treatment of Parkinson's Disease and related disorders

The basal ganglia (BG) are a set of interconnected subcortical structures t hat play a critical role in motor control. The BG are thought to control mo vements by a delicate balance of transmission through two BG circuits that connect the input and output nuclei: the direct and the indirect pathways. The BG are also involved in a number of movement disorders. Most notably, t he primary pathophysiological change that gives rise to the motor symptoms of Parkinson's Disease (PD) is the loss of dopaminergic neurons of the subs tantia nigra pars compacta (SNc) that are involved in modulating function o f the striatum and other BG structures. This ultimately results in an incre ase in activity of the indirect pathway relative to the direct pathway and the hallmark PD symptoms of rigidity, bradykinesia, and akinesia. A great d eal of effort has been dedicated to finding treatments for this disease. Th e current pharmacotherapies are aimed at replacing the missing dopamine, wh ile the current surgical treatments are aimed at reducing transmission thro ugh the indirect pathway. Dopamine replacement therapy has proven to be hel pful, but is associated with severe side effects that limit treatment and a loss of efficacy with progression of the disease. Recently developed surgi cal therapies have been highly effective, but are highly invasive, expensiv e, and assessable to a small minority of patients. For these reasons, new e ffort has been dedicated to finding pharmacological treatment options that will be effective in reducing transmission through the indirect pathway. Me mbers of the metabotropic glutamate receptor (mGluR) family have emerged as interesting and promising targets for such a treatment. This review will e xplore the most recent advances in the understanding of mGluR localization and function in the BG motor circuit and the implications of those findings for the potential therapeutic role of mGluR-targeted compounds for PD. (C) 2001 Elsevier Science Inc. All rights reserved.