ONTOGENY OF HUMAN BRAIN DOPAMINE-RECEPTORS - I - DIFFERENTIAL EXPRESSION OF [H-3]-SCH23390 AND [H-3]-YM09151-2 SPECIFIC BINDING

Dopamine receptor expression in human fetal forebrain (between 6 and 2 0 weeks of gestation) was measured using tissue-slice receptor autorad iography with the D-1-like and D-2-like antagonists [H-3]-SCH23390 and [H-3]-YM09151-2, respectively, Tissue sections were assayed in satura tion studies and examined for age-and sex-related changes in B-max. We made the following observations: (1) the ages at which D-1- and D-2-l ike receptors were first expressed in whole forebrain sections could b e reliably identified but were not significantly different from one an other (gestational age 65 days for D-1- vs. 72 days for D-2-like recep tors); (2) age-related increases in both D-1- and D-2-like receptors w ere demonstrated in forebrain and, from the middle of the first to the middle of the second trimester, the B-max for each Ligand increased b y an order of magnitude after the onset of the specific binding site's expression; (3) age-related increases in D-1-like receptors, but not D-2-like receptors, could be demonstrated in cortex; and, (4) in one c ase of trisomy 18, the B-max for [H-3]-SCH23390 was significantly elev ated above the 95% confidence interval when compared to an age-regress ed normal sample. Although D-2-like receptor density significantly inc reased with age in forebrain, age-regressed changes in D-2-like recept or expression in cortex and striatum did not reach statistical signifi cance. Likewise, a comparison of the mean B-max's by sex for both liga nds in midgestational striatum failed to reach significance. These dat a corroborate the findings of other investigators who have delineated the ontogeny of dopaminergic systems in other animal species. The regi onal differences in the expression of dopamine receptor families may b e relevant to the role which dopamine may play during normal gestation al brain development. Moreover, significant deviations in dopamine rec eptor 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 fun ctioning. (C) 1998 Elsevier Science B.V.