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 cognitive processing. Dopamine exerts effects through dopamine receptors, which are predominantly of the D-1 and D-2 subtypes in the basal ganglia. Cocaine acts as a stimulant of dopamine receptors and may cause long-term abnormalities in children exposed in utero. Dopamine receptor (primarily D-1) stimulation has been linked to gene regulation. Therefore, 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 were 7-15 times greater in the perinatal cases than in the adult. Pallidal D-2 receptor densities were similar at both ages. In both the adult and perinatal striatum, D-2 receptor densities were greater in the putamen than in the caudate, and both D-1 and D-2 receptor densities were modestly enriched in caudate striosomes compared with the matrix. In both caudate and putamen, perinatal D-1 receptor levels were within the adult range, whereas D-2 receptor levels were only 50% of adult values. The development of D-1 and D-2 receptors appears to vary across the major subdivisions of the human basal ganglia. The facts that we found such extremely high levels of D-1 receptors in the perinatal pallidum, and that D-1 receptor activation influences gene regulation, suggest that the globus pallidus could be particularly susceptible to long-term changes with perinatal exposure to cocaine and other D-1 receptor agonists or antagonists.