The distribution of excitatory amino acid receptors in the normal human midbrain and basal ganglia with implications for Parkinson's disease: a quantitative autoradiographic study using [3H]MK-801, [3H]glycine, [3H]CNQX and [3H]kainate

Abstract

Quantitative receptor autoradiography using [3H]MK-801, [3H]glycine, [3H]CNQX and [3H]kainate was employed to determine the distribution and density of excitatory amino acid (EAA) binding sites in the midbrain and basal ganglia of the normal human nervous system. Detailed knowledge of the anatomy and subtype specificity of glutamate receptors is important both in understanding the normal physiology of basal ganglia neurotransmission and the pathophysiological changes occurring in diseases affecting the basal ganglia such as Parkinson's disease (PD). In PD, glutamate receptor activation may contribute to cell death of dopaminergic neurones in the substantia nigra. In addition, perturbation of glutamate neurotransmission resulting from dopamine depletion in the basal ganglia is likely to contribute to the clinical manifestations of motor dysfunction. The distribution and density of ligand binding representing N-methyl-D-aspartate (NMDA), AMPA (2-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptors has a heterogeneous distribution in the human midbrain and basal ganglia. In the substantia nigra relatively high densities of [3H]MK-801 and strychnine-insensitive [3H]glycine binding sites representing NMDA receptors were present, whereas only moderate densities of [3H]CNQX and [3H]kainate binding sites were present, compared to other regions. In both the medial globus pallidus and subthalamic nucleus, binding sites representing NMDA, AMPA and kainate receptors were all present at low density. These findings suggest that the clinical usefulness of modifying glutamatergic neurotransmission in these basal ganglia nuclei may be limited by the relatively low density of EAA binding sites present.