Alterations in the turnover rate of dopamine D1 but not D2 receptors in the adult rat neostriatum after a neonatal dopamine denervation

• Published in: Neurochemistry international Vol. 30; no. 6; pp. 613 - 621
• Main Authors: Dewar, Karen M, Paquet, Maryse, Reader, Tomás A
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-06-1997; Elsevier
• Subjects: Aging; Animals; Animals, Newborn; Benzazepines - metabolism; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Denervation; Dopamine - metabolism; Dopamine Antagonists - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Injections, Intraventricular; Kinetics; Neostriatum - metabolism; Oxidopamine - pharmacology; Quinolines - pharmacology; Raclopride; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - metabolism; Salicylamides - metabolism; Tritium; Vertebrates: nervous system and sense organs; Dopamine; Rat; Rodentia; Central nervous system; D1 Dopamine receptor; Basal ganglion; Corpus striatum; Catecholamine; Vertebrata; Mammalia; D2 Dopamine receptor; Turnover; Neurotransmitter; Brain (vertebrata); Denervation
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/S0197-0186(96)00069-1

Adult rats that were treated with intracerebral ventricular injection of 6-hydroxydopamine (6-OHDA) as neonates exhibit a profound loss of nigrostriatal dopamine innervation in addition to a variety of other neurochemical and anatomical changes, including alterations in the number of neostriatal D1 and D2 receptor binding sites. In the present study, the turnover of neostriatal dopamine D1 and D2 receptors was measured in rats previously treated with 6-OHDA or ascorbic acid vehicle as neonates at various time intervals after peripheral
N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10
mg/kg) administration. Dopamine receptors were labelled with [
3H]SCH23390 (D1) and [
3H]raclopride (D2), while the degree of dopamine denervation was assessed by the measurement of neostriatal dopamine, homovanillic acid and dihydroxyphenylacetic acid content. Two days after acute EEDQ treatment, the maximal binding capacity (
B
max) of [
3H]SCH23390 and [
3H]raclopride binding was significantly decreased to 58 and 32% of control values, respectively, without any significant alteration in their equilibrium dissociation constants (
K
d). A time-dependent increase in the density of [
3H]SCH23390 and [
3H]raclopride binding was observed in both treatment groups following a single dose of EEDQ. The rate of recovery of D1 receptors was significantly slower in the 6-OHDA-lesioned animals as compared to controls with a half-life of 103 compared to 53
h, respectively. No differences were observed in the rate of recovery of D2 receptors in these two treatment groups. These data are consistent with the findings of decreased expression of D1 receptors in neonatal 6-OHDA-lesioned rats owing to decreased receptor synthesis, and further suggest that in this model the up-regulation of D2 receptors is a result of a post-transcriptional mechanism, such as an increased rate of post-synthetic maturation.