IDENTIFICATION OF EXTRASTRIATAL DOPAMINE D2 RECEPTORS IN POSTMORTEM HUMAN BRAIN WITH [I-125] EPIDEPRIDE

The regional distribution of striatal and extrastriatal dopamine D2 re ceptors in human brain was studied in vitro with inyl)methyl]-5-[I-125 ]iodo-2,3-dimethoxybenzamide, [I-125]epidepride, using Post mortem bra in specimens from six subjects. Scatchard analysis of the saturation e quilibrium binding in twenty-three regions of post mortem brain reveal ed highest levels of binding in the caudate (16.5 pmol/g tissue) and p utamen (16.6 pmol/g tissue) with lower levels seen in the globus palli dus (7.0 pmol/g tissue), nucleus accumbens (7.2 pmol/g tissue), hypoth alamus (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 D2 receptors in the four thalamic nu clei studied, i.e. anterior nucleus (1.0 pmol/g tissue), dorsomedial n ucleus (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 anterio r cingulate (0.26 pmol/g tissue) or anterior hippocampus (0.36 pmol/g tissue). The frontal cortex had very low levels of dopamine D2 recepto rs (0.17-0.20 pmol/g tissue) while the inferior and medial temporal co rtex had relatively higher levels (0.31-0.46 pmol/g tissue). Inhibitio n of [I-125]epidepride binding by a variety of neurotransmitter ligand s to striatal, ventral thalamic and inferior temporal cortical homogen ates demonstrated that [I-125]epidepride binding was potently inhibite d only by dopamine D2 ligands. The present study demonstrates that dop amine D2 receptors are present in basal ganglia, many limbic regions, cortex and in the thalamus. The density of thalamic D2 receptors is co mparable to many limbic regions and is considerably higher than in cor -tex. Very few frontal lobe D2 receptors are present in man.