ABSTRACT
Degeneration ...........................................................................................10 1.7 Modulation of Basal Ganglia Neurotransmission by Group II mGluRs ........ 11
1.7.1 Striatum .............................................................................................. 11 1.7.2 GPe and STN ...................................................................................... 13 1.7.3 SNr ...................................................................................................... 13
1.8 Group II mGluR Agonists in Animal Models of PD ...................................... 14 1.9 Group II mGluR-Mediated Protection against Nigrostriatal
Degeneration .............................................................................................16 1.10 Modulation of Basal Ganglia Neurotransmission by Group III mGluRs ....... 16
1.10.1 Dopaminergic Modulation of Group III mGluRs ............................... 18 1.10.2 Group III mGluR Modulation of Dopamine ...................................... 18
1.11 Group III mGluR Agonists in Animal Models of PD .................................... 19 1.12 Group III mGluR-Mediated Protection against Nigrostriatal Degeneration ...20 1.13 Concluding Remarks ......................................................................................20 References ................................................................................................................ 21
The basal ganglia are a group of interconnected subcortical nuclei that play critical roles in motor activity. Alterations in normal basal ganglia neurotransmission in disease states such as Parkinson’s disease (PD) cause dramatic impairments of normal motor function. Metabotropic glutamate receptors (mGluRs) are an important class of G protein-coupled receptors (GPCRs) that modulate both excitatory and inhibitory transmission through the basal ganglia motor circuit. In recent years, mGluRs have been implicated as exciting new targets for the treatment of both motor symptoms and neurodegeneration in PD. Because the primary pathology underlying PD is the selective loss of dopamine neurons of the substantia nigra pars compacta (SNc), the signi’cance of dopaminergic modulation of mGluR function in the basal ganglia has become increasingly appreciated. Importantly, changes in mGluR function in the absence of dopamine could impact the therapeutic potential of drugs targeting these receptors. In addition, aberrant mGluR function in the absence of dopamine could contribute to the changes in neurotransmission underlying the pathogenesis of PD symptoms. This chapter explores the physiological roles of mGluRs in the basal ganglia motor circuit, the changes in mGluR function in the absence of dopaminergic modulation, the regulation of dopaminergic transmission by mGluRs, and the signi’cance of mGluR-dopamine interactions to PD pathophysiology and therapeutics.
