Ontogeny of [3H]-SCH23390 and [3H]-YM09151-2 binding sites in human fetal forebrain.
In order to determine the gestational age at which binding sites for the dopamine "D1-like" and "D2-like" receptor antagonists, [3H]-SCH23390 and [3H]-YM09151-2, respectively, can be reliably detected in the human and to identify any discrete anatomic distribution of these binding sites, fetal forebrain tissue sections from mid-first (n = 4) and mid-second (n = 4) trimester gestations were used for receptor autoradiography. Specific binding for both ligands was detectable at the earliest fetal age examined (gestational week 6). Age-related increases in maximum saturation binding were demonstrated for both ligands using tissue sections from basal forebrain. The Bmax for both [3H]-SCH23390 and [3H]-YM09151-2 binding increased ten-fold comparing gestational week 6 and gestational week 18 values. In the cortex at gestational day 120, [3H]-YM09151-2 specific binding could be seen at the gray-white matter boundary, which was more prominent by gestational day 140. In contrast, [3H]-SCH23390 specific binding to the cortex at gestational 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 "D2-like" binding sites can be localized in a discrete cortical area in the course of normal human brain development. Characterizing these binding sites and the population of cells that demonstrates these binding sites may be relevant to neurodevelopmental hypotheses of psychiatric disorders.
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Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle 98195.
D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D001345:Autoradiography; D001549:Benzamides / Q000493:pharmacokinetics*; D001552:Benzazepines / Q000493:pharmacokinetics*; D046508:Culture Techniques; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D016548:Prosencephalon / Q000196:embryology*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*
D014150:Antipsychotic Agents; D001549:Benzamides; D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C030265:nemonapride