Age-dependent differences in the rate of recovery of striatal dopamine D₁ and D₂ receptors after inactivation with EEDQ

Recovery of striatal dopamine D₁ and D₂ binding sites in 10-, 16-, and 39-day-old rats was measured 1, 2, 4, and 8 days after irreversible antagonism with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Ontogenetic and EEDQ-induced changes in D₁ and D₂ binding sites were determined by Scatchard analyses using six concentrations of either [³H]SCH 23390 or [³H]spiperone. Twenty-four hours after EEDQ (7.5 mg/kg) treatment, a significant depletion of both dopamine D₁ and D₂ receptors was found for all age groups; however, the magnitude of the depletion was greater in 39-day-old rats than in the two preweanling age groups. Both 16- and 39-day-old rats showed significant recovery of dopamine D₁ and D₂ receptors by the eighth day after EEDQ treatment, but the 16-day-old rats showed a faster recovery of dopamine D₁ receptors than did the 39-day-olds. Unexpectedly, 10-day-old rats did not show any evidence of receptor recovery, as the percent control values for these animals did not change across the 8-day recovery period. Pretreatment with the dopamine D₁ receptor antagonist SCH 23390 and the dopamine D₂ receptor antagonist sulpiride was sufficient to protect dopamine D₁ and D₂ receptors from EEDQ-induced inactivation. Protein values and receptor affinity (pK_d values) were not affected by EEDQ treatment at any of the ages tested. Therefore, these results indicated that the rate of dopamine receptor repopulation varies across ontogeny, with 10-day-old rats exhibiting slower recovery than older rat pups or postweanling rats.