Age-related differential recovery rates of rat striatal D-1 dopamine receptors following irreversible inactivation.
We report here the effects of age on the steady state levels of [3H]flupentixol-labeled striatal D-1 dopamine receptors and their recovery rates following irreversible blockade in mature (4 months old) and senescent (28 months old) male Fischer 344 rats. Senescent rats exhibited significantly reduced (-22%) Bmax levels of D-1 dopamine receptors compared with their mature counterparts. In addition, the time course of recovery of D-1 dopamine receptors following irreversible receptor inactivation by a single injection of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was significantly slower in senescent animals. This slower recovery rate was the result of decreases in both receptor production rate and receptor degradation rate constants compared with mature rats. Although EEDQ irreversibly inactivated D-1 dopamine receptors, it was without effect on dopamine uptake sites. A chronic, 21 day reserpine treatment did not significantly alter the Bmax nor the rate of recovery of D-1 dopamine receptors with respect to values in age-matched non-reserpine-treated rats. These data indicate that both the steady state levels of striatal D-1 dopamine receptors and the 'turnover' of these receptors are significantly affected as a consequence of natural aging.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D005475:Flupenthixol / Q000493:pharmacokinetics; D008297:Male; D008454:Mazindol / Q000493:pharmacokinetics; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D012110:Reserpine / Q000008:administration & dosage; D014793:Visual Cortex / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D011804:Quinolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; C000470:EEDQ; D012110:Reserpine; D008454:Mazindol; D005475:Flupenthixol