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 (pKd values) were not affected by EEDQ treatment at any of the ages tested. Therefore, these results indicate 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.
Crawford
C A
CA
Department of Psychology, University of Kentucky, Lexington 40506.
Rowlett
J K
JK
McDougall
S A
SA
Bardo
M T
MT
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013134:Spiperone
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D009419:Nerve Tissue Proteins; D011804:Quinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; C000470:EEDQ