Quantitative analysis of the dopamine D4 receptor in the mouse brain

The D4 receptor (D4R), a member of the dopamine D2-like receptor family, ha s been implicated in the pathophysiology of several diseases and has been t he target of various investigations regarding its distribution and quantifi cation. The brain distribution of the D4R has been well described in variou s species, but the quantification is still an issue of controversy, because no specific ligand is commercially available. To circumvent this difficult y we have performed a biochemical and autoradiographical study in brain sam ples obtained from mice lacking D4Rs and their wild-type siblings; comparis on of their binding parameters allows a more accurate quantification of the members of the D2-like receptor family (D2, D3, and D4 receptors). We foun d that the distribution of D2-like receptors in mouse brain is similar to t hat of rat brain, i.e., caudate putamen, nucleus accumbens, olfactory tuber cle, and hippocampus. The contribution of the D4R to the overall population of D2-like receptors is 17% in nucleus accumbens, 21% in caudate putamen a nd olfactory tubercle, and 40% in hippocampus. Based on our study we conclu de that nemonapride probably binds to nondopaminergic sites that if not pro perly blocked may lead to overestimations of D4R levels. We observed that t he experimental condition that better estimates the density of D4 receptors is the displacement of D2 and D3 [H-3]nemonapride binding sites with cold raclopride. (C) 2000 Wiley-Liss, Inc.