Identification of extrastriatal dopamine D2 receptors in post mortem human brain with [125I]epidepride

Abstract The regional distribution of striatal and extrastriatal dopamine D 2 receptors in human brain was studied in vitro with( S )- N -[(1-ethyl-2-pyrrolidinyl)methyl]-5-[ 125 I]iodo-2,3-dimethoxybenzamide, [ 125 I]epidepride, using post mortem brain specimens from six subjects. Scatchard analysis of the saturation equilibrium binding in twenty-three regions of post mortem brain revealed highest levels of binding in the caudate (16.5 pmol/g tissue) and putamen (16.6 pmol/g tissue) with lower levels seen in the globus pallidus (7.0 pmol/g tissue), nucleus accumbens (7.2 pmol/g tissue), hypothalamus (1.8 pmol/g tissue), pituitary (1.3 pmol/g tissue), substantia innominata (1.0 pmol/g tissue), and amygdala (0.87 pmol/g tissue). Of note was the presence of dopamine D 2 receptors in the four thalamic nuclei studied, i.e. anterior nucleus (1.0 pmol/g tissue), dorsomedial nucleus (0.96 pmol/g tissue), ventral nuclei (0.72 pmol/g tissue), and pulvinar (0.86 pmol/g tissue), at levels comparable to the amygdala (0.87 pmol/g tissue) and considerably higher than levels seen in anterior cingulate (0.26 pmol/g tissue) or anterior hippocampus (0.36 pmol/g tissue). The frontal cortex had very low levels of dopamine D 2 receptors (0.17–0.20 pmol/g tissue) while the inferior and medial temporal cortex had relatively higher levels (0.31–0.46 pmol/g tissue). Inhibition of [ 125 I]epidepride binding by a variety of neurotransmitter ligands to striatal, ventral thalamic and inferior temporal cortical homogenates demonstrated that [ 125 I]epidepride binding was potently inhibited only by dopamine D 2 ligands. The present study demonstrates that dopamine D 2 receptors are present in basal ganglia, many limbic regions, cortex and in the thalamus. The density of thalamic D 2 receptors is comparable to many limbic regions and is considerably higher than in cortex. Very few frontal lobe D 2 receptors are present in man.