Regional distribution of dopamine D4 receptors in rat forebrain

Binding of the D2-like (D2/D3/D4) radioligand [3H]nemonapride under selective conditions (with 300 nM S[-]-raclopride and other masking agents to occlude D2/D3 receptors and non-specific binding sites) revealed a subset of raclopride-insensitive binding sites considered D4-like receptors. These sites were stereoselective to R(-)-N-n-propylnorapomorphine (NPA) over its S(+)-NPA in a similar fashion to cloned D4 receptors expressed in cell lines. In addition, the highly D4-selective agent L-745,870 displaced 74-83% of these sites in rat brain regions, suggesting that most were D4 receptors. These apparent D4 receptors represented a relatively high proportion of D2-like receptors in hippocampus, dorsolateral frontal, medial prefrontal and entorhinal cortex, but fewer in caudate-putamen and nucleus accumbens.