IN-VIVO LABELING OF SIGMA-RECEPTORS IN MOUSE-BRAIN WITH [H-3] 4-PHENYL-1-(4-PHENYLBUTYL)PIPERIDINE

4-Phenyl-1-(4-phenylbutyl)piperidine (4-PPBP) is a very potent ligand for sigma (Sigma) receptors. The present study was undertaken to evaluate [H-3]4-PPBP as a radioligand for in vivo labeling of cerebral sigma receptors. After intravenous administration of [H-3]4-PPBP to mice, there is high uptake of radioactivity in the brain. The regional distribution of radioactivity in the brain 2 h after intravenous injection of [H-3]4-PPBP parallels the in vitro binding of the radioligand in rat brain (pons/medulla > cerebellum greater than or equal to prefrontal cortex greater than or equal to parietal cortex > hypothalamus > olfactory tubercle greater than or equal to thalamus > hippocampus > striatum). Pretreatment with haloperidol(2 mg/ kg) significantly decreases the radioactivity measured in the brain 30-120 min after injection of [H-3]4-PPBP. Pretreatment with unlabeled 4-PPBP or ifenprodil also significantly decreases radioactivity in the brain 2 h after injection of [H-3]4-PPBP, in a dose-dependent manner. The in vivo binding of [H-3]4-PPBP in the brain also is significantly inhibited by SL 82.0715, BMY 14802, 1,3-di-o-tolylguanidine (DTG), and (+)-enantiomers of pentazocine, SKF 10,047, and 3-PPP, but not by the corresponding (-)-enantiomers, consistent with stereoselectivity of inhibition obtained in in vitro binding studies. In contrast, pretreatment with dizocilpine and spiperone does not inhibit in vivo binding of[H-3]4-PPBP. The results indicate that [H-3]4-PPBP would be a suitable radioligand for in vivo labeling of a receptors in brain. (C) 1995 Wiley-Liss, Inc.