CONCENTRATION AND DISTRIBUTION OF [H-3] SCH23390 AND [H-3] YM09151-2 BINDING-SITES IN MIDGESTATIONAL HUMAN FETAL CORTEX

Binding sites for the dopamine receptor antagonists [H-3]-SCH23390 and [H-3]-YM09151-2 have been demonstrated in human fetal forebrain at th e sixth gestational week and appear to increase in concentration in an age-related fashion throughout the first trimester. Using the techniq ues of receptor autoradiography with midsecond trimester human fetal c ortex (gestational weeks 17 and 20), the distribution and concentratio n of binding sites for these radiolabeled ligands were compared. Satur able [H-3]-SCH23390 specific binding was demonstrated in the cortical plate of the tissue obtained at gestational week 17 (K-D = 0.16 nM, B- MAX = 0.005 fmol/mm(2)). Although saturable binding for [H-3]-SCH23390 could be demonstrated in the cortical plate at gestational week 20 (K -D = 2.35 nM, B-MAX = 0.008 fmol/mm(2)), image subtraction revealed sp ecific binding in the intermediate zone as well. Saturable [H-3]-YM091 51-2 specific binding was likewise demonstrated in the cortical plate at gestational week 17 (K-D = 0.36 nM, B-MAX = 0.044 fmol/mm(2)). At g estational week 20, specific and saturable [H-3]-YM09151-2 binding app eared to be stratified in the subplate zone, between the cortical plat e and the intermediate zone (K-D = 2.02 nM, B-MAX = 0.076 fmol/mm(2)). These data suggest that specific, saturable binding for dopamine rece ptor antagonists can be demonstrated in human cortex by the completion of corticogenesis and at the earliest stages of cortical differentiat ion. The cells that express these binding sites may play a role in dev eloping forebrain dopaminergic neuronal systems, the disturbance of wh ich may be relevant to adult psychopathology.