Selective in vivo binding of [³H]naltriben to δ-opioid receptors in mouse brain

Naltriben (NTB) is a selective antagonist for the putative δ₂-opioid receptor. We have determined the regional kinetics and pharmacological profile of [³H]naltriben in vivo in mouse brain. After i.v. administration to CD1 mice, [³H]naltriben uptake and retention were high in striatum, cortical regions and olfactory tubercles, and low in superior colliculi and cerebellu. Robust rank order correlation was found between [³H]naltriben uptake in discrete brain regions and prior δ-opioid receptor binding determinations in vitro and in vivo [³H]Naltriben binding in vivo was saturable, and was blocked by the δ-opioid receptor antagonist naltrindole, but not by the μ-opioid receptor antagonist cyprodime or the κ-opioid receptor agonist (trans)-(±)-3,4-dicholoro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide mesylate (U50, 488H). (E)-7- Benzylidenenaltrexone (BNTX), a selective antagonist for the putative δ₁- opioid receptor, was 9.6- to 12.9-fold less potent than naltriben as an inhibitor of [³H]naltriben binding. Thus, the sites labeled by [³H]naltriben in vivo may correspond to the δ₂-opioid receptor subtype. Such assignment is not definitive, particularly considering the 4-fold higher brain uptake of naltriben as compared to (E)-7-benzylidenenaltrexone. Moreover, the regional distribution of [³H]naltriben in brains from CXB- 7/BY (CXBK) mice, a strain that shows supraspinal δ₁- but not δ₂-opioid receptor agonist effects, was quite similar to that found for CD1 mice.