Density of NMDA‐Coupled and Uncoupled 1‐[1‐(2‐[³H]Thienyl)cyclohexyl]piperidine Recognition Sites in the Brain and Spinal Cord: Differential Effects of NMDA Agonists and Antagonists

Abstract: Binding of 1‐[1‐(2‐[³H]thienyl)cyclohexyl]piperidine ([³H]TCP) to mouse brain and spinal cord membranes was studied using compounds selective for the NMDA‐coupled 1‐(1‐phenylcyclohexyl)piperidine (PCP) and/or σ recognition sites. In both tissues, [³H]TCP labeled two populations of binding sites. Density of the low‐affinity sites was approximately the same in both tissues, but the population of the high‐affinity [³H]TCP sites was three times bigger in the brain than in the spinal cord. Self‐ and cross‐displacement studies showed that the high‐affinity [³H]TCP binding sites could be identical with NMDA receptor‐coupled PCP sites, whereas the low‐affinity [³H]TCP sites may be associated with σ binding sites in both tissues. The NMDA‐coupled PCP sites labeled in the presence of 6.25 nM [³H]TCP constituted a much higher percentage of the total binding in the brain (75%) than in the spinal cord (44%). Consistent with this, reintroduction of glycine and glutamate significantly increased, but DA antagonists significantly inhibited [³H]TCP binding in the brain but not in the spinal cord. Together, these data suggest that a large component of [³H]TCP‐labeled binding sites in the spinal cord may be associated with σ but not the NMDA receptor‐coupled PCP sites.