Regional distribution of dopamine D-4 receptors in rat forebrain

BINDING of the D-2-like (D-2/D-3/D-4) radioligand [H-3]nemonapride under selective conditions (with 300 nM S[-]-raclopride and other masking agents to occlude D-2/D-3 receptors and non-specific binding sites) revealed a subset of raclopride-insensitive binding sites considered D-4-like receptors. These sites were stereoselective to R(-)-N-n-propylnorapomorphine (NPA) over its S(+)-NPA in a similar fashion to cloned D-4 receptors expressed in cell lines. In addition, the highly D-4-selective agent L-745,870 displaced 74-83% of these sites in rat brain regions, suggesting that most were D-4 receptors. These apparent D-4 receptors represented a relatively high proportion of D-2-like receptors in hippocampus, dorsolateral frontal, medial prefrontal and entorhinal cortex, but fewer in caudate-putamen and nucleus accumbens.