D-1 AND D-2 DOPAMINE-RECEPTORS IN PERINATAL AND ADULT BASAL GANGLIA

There is reason to believe that dopamine is important in developmental programs of the basal ganglia, brain nuclei implicated in motor and c ognitive processing. Dopamine exerts effects through dopamine receptor s, which are predominantly of the D-1 and D-2 subtypes in the basal ga nglia. Cocaine acts as a stimulant of dopamine receptors and may cause long-term abnormalities in children exposed in utero. Dopamine recept or (primarily D-1) stimulation has been linked to gene regulation. The refore, D-1 and D-2 receptor densities in perinatal and adult striatum and globus pallidus were examined using quantitative autoradiography. The most striking finding was that pallidal D-1 receptor densities we re 7-15 times greater in the perinatal cases than in the adult. Pallid al D-2 receptor densities were similar at both ages. In both the adult and perinatal striatum, D-2 receptor densities were greater in the pu tamen than in the caudate, and both D-1 and D-2 receptor densities wer e modestly enriched in caudate striosomes compared with the matrix. In both caudate and putamen, perinatal D-1 receptor levels were within t he adult range, whereas D-2 receptor levels were only 50% of adult val ues. The development of D-1 and D-2 receptors appears to vary across t he major subdivisions of the human basal ganglia. The facts that we fo und such extremely high levels of D-1 receptors in the perinatal palli dum, and that D-1 receptor activation influences gene regulation, sugg est that the globus pallidus could be particularly susceptible to long -term changes with perinatal exposure to cocaine and other D-1 recepto r agonists or antagonists.