Modulation of basal ganglia group II
metabotropic glutamate receptors (
mGluR2/3) is a potential therapeutic alternative to
levodopa in
Parkinson disease (PD). We used receptor-binding autoradiography of the
mGluR2/3-selective radioligand [H]
LY341495 in postmortem brain specimens from PD patients (n = 14) and controls (n=11) to investigate possible contributions of changes in
ligand binding of this receptor to
levodopa-associated motor complications experienced premortem in PD patients. The PD patients included those with and without histories of
dyskinesias and those with and without "wearing off," which is defined as a reduced period of benefit from
levodopa. Specific binding of [H]
LY341495 to
mGluR2/3 in the basal ganglia was higher in the caudate nucleus than the putamen and lower by approximately half in the external and internal globus pallidus (GPi) in controls. [H]
LY341495-specific binding was reduced in the caudate and GPi in patients without wearing-off (-22% caudate, -30% GPi), compared with controls and with patients who had experienced wearing-off; there were no differences among PD patients with or without
dyskinesias. These data suggest that an adaptive downregulation of
mGluR2/3 in PD patients without wearing-off may compensate for increased
glutamate. They indicate a key role for
mGluR2/3 in control of movement and the potential for
mGluR2/3-targeted drugs in the management of wearing-off fluctuations in PD.