Presence of D4 dopamine receptors in human prefrontal cortex: a postmortem study

The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [3H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component.

Frontal cortex samples were harvested postmortem, during autopsy sessions, from 5 subjects. In the first assay, tissue homogenates were incubated with increasing concentrations of [3H]YM-09151-2, whereas L-745870, which has a high affinity for D4 and a low affinity for D2/D3 receptors, was used as the displacer. In the second assay, raclopride, which has a high affinity for D2/D3 receptors and a low affinity for D4 receptors, was used to block D2/D3. The L-745870 (500 nM) was added to both assays in order to determine the nonspecific binding.

Our experiments revealed the presence of specific and saturable binding of [3H]YM-09151-2. The blockade of D2 and D3 receptors with raclopride ensured that the D4 receptors were labeled. The mean maximum binding capacity was 88 +/- 25 fmol/mg protein, and the dissociation constant was 0.8 +/- 0.4 nM.

Our findings, although not conclusive, suggest that the density of D4 receptors is low in the human prefrontal cortex.