Concentration and distribution of [3H]-SCH23390 and [3H]-YM09151-2 binding sites in midgestational human fetal cortex.
Binding sites for the dopamine receptor antagonists [3H]-SCH23390 and [3H]-YM09151-2 have been demonstrated in human fetal forebrain at the sixth gestational week and appear to increase in concentration in an age-related fashion throughout the first trimester. Using the techniques of receptor autoradiography with midsecond trimester human fetal cortex (gestational weeks 17 and 20), the distribution and concentration of binding sites for these radiolabeled ligands were compared. Saturable [3H]-SCH23390 specific binding was demonstrated in the cortical plate of the tissue obtained at gestational week 17 (KD = 0.16 nM, BMAX = 0.005 fmol/mm2). Although saturable binding for [3H]-SCH23390 could be demonstrated in the cortical plate at gestational week 20 (KD = 2.35 nM, BMAX = 0.008 fmol/mm2), image subtraction revealed specific binding in the intermediate zone as well. Saturable [3H]-YM09151-2 specific binding was likewise demonstrated in the cortical plate at gestational week 17 (KD = 0.36 nM, BMAX = 0.044 fmol/mm2). At gestational week 20, specific and saturable [3H]-YM09151-2 binding appeared to be stratified in the subplate zone, between the cortical plate and the intermediate zone (KD = 2.02 nM, BMAX = 0.076 fmol/mm2). These data suggest that specific, saturable binding for dopamine receptor antagonists can be demonstrated in human cortex by the completion of corticogenesis and at the earliest stages of cortical differentiation. The cells that express these binding sites may play a role in developing forebrain dopaminergic neuronal systems, the disturbance of which may be relevant to adult psychopathology.
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Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle 98195.
D001549:Benzamides / Q000493:pharmacokinetics*; D001552:Benzazepines / Q000493:pharmacokinetics*; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*
D001549:Benzamides; D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; C030265:nemonapride