Dopamine D₁ receptor development depends on endogenous dopamine

Profound depletion of forebrain dopamine by 6-hydroxydopamine in neonatal rats (day 3) was associated with up to 82% loss of D₁ receptor sites labeled with [³H]SCH-23390 at day 21. Administration of the selective D₁ agonist SKF-38393 (days 6-18) abolished the correlation between D₁ receptor density and DA concentrations, even with >99% depletion of DA. In intact control animals, there was an inverse correlation between spontaneous variation in levels of DA and D₁ receptor site density in forebrain tissue (r = -0.79) which also was abolished by treatment with the D₁ agonist. Thus, D₁ receptor density may be regulated by reciprocal regulatory processes during normal development, but may fail to develop in the absence of an adequate level of stimulation.