ONTOGENY OF [H-3] SCH23390 AND [H-3] YM09151-2 BINDING-SITES IN HUMANFETAL FOREBRAIN

In order to determine the gestational age at which binding sites for t he dopamine ''D-1-like'' and ''D-2-like'' receptor antagonists, [H-3]- SCH23390 and [H-3]-YM09151-2, respectively, can be reliably detected i n the human and to identify any discrete anatomic distribution of thes e binding sites, fetal forebrain tissue sections from mid-first (n = 4 ) and mid-second (n = 4) trimester gestations were used for receptor a utoradiography. Specific binding for both ligands was detectable at th e earliest fetal age examined (gestational week 6). Age-related increa ses in maximum saturation binding were demonstrated for both ligands u sing tissue sections from basal forebrain. The B-max for both [H-3]-SC H23390 and [H-3]-YM09151-2 binding increased ten-fold comparing gestat ional week 6 and gestational week 18 values. In the cortex at gestatio nal day 120, [H-3]-YM09151-2 specific binding could be seen at the gra y-white matter boundary, which was more prominent by gestational day 1 40. In contrast, [H-3]-SCH23390 specific binding to the cortex at gest ational day 120 did not appear to differentiate specific areas and did not increase between gestational days 120 and 140. These preliminary observations in human fetal brain provide evidence that dopamine ''D-2 -like'' binding sites can be localized in a discrete cortical area in the course of normal human brain development. Characterizing these bin ding sites and the population of cells that demonstrates these binding sites may be relevant to neurodevelopmental hypotheses of psychiatric disorders.