ALTERATIONS IN THE TURNOVER RATE OF DOPAMINE D1 BUT NOT D2 RECEPTORS IN THE ADULT-RAT NEOSTRIATUM AFTER A NEONATAL DOPAMINE DENERVATION

Adult rats that were treated with intracerebral ventricular injection of 6-hydroxydopamine (6-OHDA) as neonates exhibit a profound loss of n igrostriatal dopamine innervation in addition to a variety of other ne urochemical and anatomical changes, including alterations in the numbe r of neostriatal D1 and D2 receptor binding sites. In the present stud y, the turnover of neostriatal dopamine D1 and D2 receptors was measur ed 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 [H-3]SCH23390 (D1) and [H-3]raclopride ( D2), while the degree of dopamine denervation was assessed by the meas urement of neostriatal dopamine, homovanillic acid and dihydroxyphenyl acetic acid content. Two days after acute EEDQ treatment, the maximal binding capacity (B-max) of [H-3]SCH23390 and [H-3]raclopride binding was significantly decreased to 58 and 32% of control values, respectiv ely, without any significant alteration in their equilibrium dissociat ion constants (K-d). A time-dependent increase in the density of [H-3] SCH23390 and [H-3]raclopride binding was observed in both treatment gr oups following a single dose of EEDQ. The rate of recovery of D1 recep tors was significantly slower in the 6-OHDA-lesioned animals as compar ed 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 find ings of decreased expression of D1 receptors in neonatal 6-OHDA-lesion ed rats owing to decreased receptor synthesis, and further suggest tha t in this model the up-regulation of D2 receptors is a result of a pos t-transcriptional mechanism, such as an increased rate of post-synthet ic maturation. (C) 1997 Elsevier Science Ltd.