ONTOGENY OF D-1A AND D-2 DOPAMINE-RECEPTOR SUBTYPES IN RAT-BRAIN USING IN-SITU HYBRIDIZATION AND RECEPTOR-BINDING

The prenatal and postnatal ontogeny of D-1A and D-2 dopamine receptors was assessed by in situ hybridization of messenger RNAs encoding the receptors and by radioligand binding autoradiography. On gestational d ay 14, signals for D-1A and D-2 dopamine receptor messages were observ ed in selected regions in ventricular and subventricular zones which c ontain dividing neuroblasts, and in intermediate zones that contain ma turing and migrating neurons. Specifically, D-1A and D-2 dopamine rece ptor message was observed in the developing caudate-putamen, olfactory tubercle, and frontal, cingulate, parietal and insular cortices. Addi tionally, D-1A dopamine receptor messenger RNA was found in the develo ping epithalamus, thalamus, hypothalamus, pens, spinal cord and neural retina; D-2 dopamine receptor messenger RNA was also observed in the mesencephalic dopaminergic nuclear complex. Gene expression of D-1A an d D-2 dopamine receptor subtypes in specific cells as they differentia te precedes dopamineplies that receptor expression is an intrinsic pro perty of these neurons. The early expression of dopamine receptor mess enger RNA suggests a regulatory role for these receptors in brain deve lopment. While the signal for both messages increased in the intermedi ate zones on gestational day 16, it decreased in the ventricular and s ubventricular zones, and was no longer apparent in these zones by gest ational day 18. By gestational day 18, abundant D-1A or D-2 dopamine r eceptor messenger RNA was observed in cell groups similar in location to those observed in the adult brain. On gestational day 18, D-1A dopa mine receptor message was noted in the neural retina, anterior olfacto ry nucleus, the insular, prefrontal, frontal, cingulate, parietal and retrosplenial cortices, the olfactory tubercle, caudate-putamen, later al habenula, dorsolateral geniculate nucleus, ventrolateral and mediol ateral thalamic nuclei, and the suprachiasmatic and ventromedial nucle i of the hypothalamus. D-2 dopamine receptor message was observed on g estational day 18 in the insular, prefrontal, Frontal and cingulate co rtices, the olfactory tubercle, caudate-putamen, ventral tegmental are a, substantia nigra, and the intermediate lobe of the pituitary. At bi rth, expression of messenger RNA for both dopamine receptor subtypes i n the striatum approximated that seen in mature rats. In contrast, D-1 A and D-2 receptor binding, measured with [H-3]SCH-23390 and [H-3]racl opride, respectively, was low at birth and progressively increased to reach adult levels between days 14 and 21. The in situ hybridization d ata showing early prenatal expression of messenger RNA for the D-1A an d D-2 dopamine receptors are consistent with the hypothesis that these receptors have a regulatory role in neuronal development. At birth, t he relatively high expression of messenger RNA for these receptors was in contrast to the relatively low density of binding sites for [H-3]S CK-23390 and [H-3]raclopride. These results suggest differences in the translational regulation of dopamine receptors at different developme ntal stages.