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In vivo labeling of sigma receptors in mouse brain with [ 3 H]4‐phenyl‐1‐(4‐phenylbutyl)piperidine
Author(s) -
Hashimoto Kenji,
Scheffel Ursula,
London Edythe D.
Publication year - 1995
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890200112
Subject(s) - sigma receptor , in vivo , radioligand , striatum , pharmacology , chemistry , receptor , medicine , biology , endocrinology , biochemistry , dopamine , microbiology and biotechnology
4‐Phenyl‐1‐(4‐phenylbutyl)piperidine(4‐PPBP) is a very potent ligand for σ (Sigma) receptors. The present study was undertaken to evaluate [ 3 H]4‐PPBPas a radioligand for in vivo labeling of cerebral σ receptors. After intravenous administration of [ 3 H]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 [ 3 H]4‐PPBP parallels the in vitro binding of the radioligand in rat brain (pons/medulla > cerebellum ≥ prefrontal cortex ≥ parietal cortex > hypothalamus > olfactory tubercle ≥ thalamus > hippocampus > striatum). Pretreatment with haloperidol (2 mg/kg) significantly decreases the radioactivity measured in the brain 30–120 min after injection of [ 3 H]4‐PPBP. Pretreatment with unlabeled 4‐PPBP or ifenprodil also significantly decreases radioactivity in the brain 2 h after injection of [ 3 H]4‐PPBP, in a dosedependent manner. The in vivo binding of [ 3 H]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 [ 3 H]4‐PPBP. The results indicate that [ 3 H]4‐PPBP would be a suitable radioligand for in vivo labeling of σ receptors in brain. © 1995 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America .