Autoradiographic study on the pharmacological characteristics of [3H]3-OH-PCP binding sites in rat brain.

The binding properties and brain distribution of a radioactive form of the compound 3-OH-PCP, a derivative of phencyclidine (PCP), were examined in rat brain tissue using autoradiography. Binding occurred with fast and slow components, and the pattern of binding matched that of other PCP receptor labels, TCP and MK-801. Highest binding was in the hippocampus and outer cerebral cortex layers, while low binding was in the brain stem and cerebellum. The binding was strongly blocked by MK-801 and 3-OH-PCP, but less so by a related compound, (+)-SKF 10047, in certain brain regions. Antagonists of the NMDA receptor complex also displaced binding similarly to MK-801, indicating the binding site is essentially the same as the PCP site labeled by TCP and MK-801.

Study at a glance

Abstract

The pharmacological characteristics and the regional distribution of [3H]3-OH-PCP (1-[1(3-hydroxyphenyl)-cyclohexyl]piperidine) binding were investigated in rat brain by quantitative autoradiography. Kinetic analysis of [3H]3-OH-PCP binding revealed fast and slow components, in the association and dissociation studies. The regional distribution of binding closely corresponded to those of binding sites labeled by [3H]N-[l-(2-thienyl)-cyclohexyl]3,4-piperidine (TCP) and [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate (MK 801). High densities of [3H]3-OH-PCP binding sites were found in the stratum radiatum and orients of field CA1 in the hippocampus and in the outer layers of cerebral cortices. In contrast, low levels of binding were seen in the brain stem and the granular cell layer of the cerebellum. [3H]3-OH-PCP binding was strongly inhibited by MK 801 and 3-OH-PCP, while the potency of (+)-SKF 10047 in inhibiting [3H]3-OH-PCP binding was less in the cerebral cortex and hippocampus. The antagonists for the glutamate, glycine and polyamine recognition sites at the NMDA/PCP receptor complex displaced [3H]3-OH-PCP binding sites with a potency similar to that of [3H]MK 801. These findings suggest that the [3H]3-OH-PCP binding site is similar or identical to the PCP binding site labeled by [3H]TCP and [3H]MK 801.