mGluRs: a target for pharmacotherapy in Parkinson disease.
Metabotropic glutamate receptors (mGluRs) are G-protein-coupled excitatory amino acid (glutamate) receptors and are abundantly expressed in basal ganglia nuclei. We used behavioral, regional glucose uptake metabolic mapping, and FOS protein expression to examine the effects of stimulating striatal and subthalamic mGluRs in rats. Stimulation of striatal Group I mGluRs produced behavioral effects mediated by polysynaptic activation of subthalamic neurons. Stimulation of subthalamic Group II mGluRs produced similar effects. Excessive activity of subthalamic neurons is a key feature of parkinsonism. mGluR Group I or Group II antagonists may prove to be useful for symptomatic treatment of parkinsonism. Stimulation of Group III mGluRs produced behavioral effects in only 6-hydroxydopamine-lesioned animals. Regional glucose uptake metabolic mapping and FOS expression studies suggested that striatal dopamine denervation produced increased sensitivity of Group III mGluRs. Agents active at Group III mGluRs may also be useful for treatment of parkinsonism.
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
Jennifer A
JA
Feeley Kearney
Roger L
RL
Albin
D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors
D000600:Amino Acids, Dicarboxylic; D018690:Excitatory Amino Acid Agonists; D016760:Proto-Oncogene Proteins c-fos; D018094:Receptors, Metabotropic Glutamate; C035261:(alpha-carboxycyclopropyl)glycine; D008734:Methoxyhydroxyphenylglycol; D016627:Oxidopamine; D005947:Glucose; C010117:3,4-dihydroxyphenylglycol