INVIVO LABELING OF PHENCYCLIDINE (PCP) RECEPTORS WITH H-3 TCP IN THE MOUSE-BRAIN

The phencyclidine (PCP) derivative N‐[1‐(2‐thienyl) cyclohexyl]‐piperidine (3H‐TCP) was used to label in vivo the N‐methyl‐D‐aspartate (NMDA) receptor‐associated ionic channel in the mouse brain. After the injection of a tracer dose of 3H‐TCP, a spread labeling throughout the brain was observed, but was the highest in the cerebellum. Preadministration of unlabeled TCP (30 mg/kg) resulted in a 90% reduction of 3H‐TCP binding. PCP, TCP, MK‐801, dexoxadrol, ketamine, and SKF 10,047 isomers dose‐dependently prevented the in vivo 3H‐TCP binding. ID50 determined in the cerebrum and the cerebellum were respectively correlated with K0.5 for 3H‐TCP high (rat cortex) and low affinity (rat cerebellum) sites in vitro. The pharmacological specificity of the 3H‐TCP binding site in the cerebellum was significantly different from that in the cerebrum. ID50 values were generally higher than in the cerebrum and, particularly, MK‐801, the most potent drug in the cerebrum, was without significant effect in the cerebellum, at any time and at doses as high as 30 mg/kg. N‐[1‐(2‐benzo(b) thiophenyl) cyclohexyl]piperidine (BTCP), desipramine, and atropine showed a more efficient prevention of 3H‐TCP binding in the cerebellum than in the cerebrum. The prevention of the binding by TCP or PCP, at doses close to their ID50 values, was rapid and then decreased slowly. The effect of MK‐801 was long‐lasting. This study confirm previous in vitro studies: 3H‐TCP is an efficient tool for the labeling of the NMDA receptor‐associated ionic channel. particularly, low affinity sites were identified in the cerebellum with the same pharmacological properties as in vitro in the same region. Copyright © 1990 Wiley‐Liss, Inc.