EVIDENCE FOR DOPAMINE-RECEPTOR PRUNING BETWEEN ADOLESCENCE AND ADULTHOOD IN STRIATUM BUT NOT NUCLEUS-ACCUMBENS

Postnatal development of dopamine D-1 and D-2 receptor families in striatum and nucleus accumbens of rats was studied at 25, 35, 40, 60, 80, 100 and 120 days using autoradiography. These ages were selected to test the hypothesis that dopamine receptors were overproduced prior to puberty (day 40), and pruned back to adult levels thereafter. This hypothesis was confirmed in striatum but not nucleus accumbens. D-1 receptor B-max ([H-3]SCH-23390) peaked at 40 days, with levels 67 +/- 21% greater than at 25 days. However, B-max levels were at least 35% lower at 60-120 days than at 40 days. Similarly, D-2 receptor numbers ([H-3]YM-09151-2) increased 144 +/- 26% between 25 and 40 days, but were reduced by 34-38% between 60-120 days. In contrast, D-1 and D-2 receptor B-max increase approximately 150% between 25 and 40 days in nucleus accumbens, levels fell slightly at 60 or 80 days, but were no different at 100 and 120 days then they were at 40 days. These findings suggest that these two major dopamine target regions follow different developmental strategies, and this has implications for etiological theories of schizophrenia that focus on anomalous receptor pruning.