Ontogeny of human brain dopamine receptors I. Differential expression of [³H]-SCH23390 and [³H]-YM09151-2 specific binding

Dopamine receptor expression in human fetal forebrain (between 6 and 20 weeks of gestation) was measured using tissue-slice receptor autoradiography with the D₁-like and D₂-like antagonists [³H]-SCH23390 and [³H]-YM09151- 2, respectively. Tissue sections were assayed in saturation studies and examined for age- and sex-related changes in B(max). We made the following observations: (1) the ages at which D₁- and D₂-like receptors were first expressed in whole forebrain sections could be reliably identified but were not significantly different from one another (gestational age 65 days for D₁- vs. 72 days for D₂-like receptors); (2) age-related increases in both D₁- and D₂-like receptors were demonstrated in forebrain and, from the middle of the first to the middle of the second trimester, the B(max) for each ligand increased by an order of magnitude after the onset of the specific binding site's expression; (3) age-related increases in D₁-like receptors, but not D₂-like receptors, could be demonstrated in cortex; and, (4) in one case of trisomy 18, the B(max) for [³H]-SCH23390 was significantly elevated above the 95% confidence interval when compared to an age-regressed normal sample. Although D₂-like receptor density significantly increased with age in forebrain, age-regressed changes in D₂-like receptor expression in cortex and striatum did not reach statistical significance. Likewise, a comparison of the mean B(max)'s by sex for both ligands in midgestational striatum failed to reach significance. These data corroborate the findings of other investigators who have delineated the ontogeny of dopaminergic systems in other animal species. The regional differences in the expression of dopamine receptor families may be relevant to the role which dopamine may play during normal gestational brain development. Moreover, significant deviations in dopamine receptor expression during gestation (as seen in this one case of trisomy 18) may signify underlying pathological processes that ultimately are manifested by abnormal psychological development and/or cognitive functioning.