Postnatal development of striatal dopamine function. II. Effects of neonatal 6-hydroxydopamine treatments on D 1 and D 2 receptors, adenylate cyclase activity and presynaptic dopamine function

Abstract

To evaluate the influence of patch and matrix ingrowth of DA terminals upon striatal DA (dopamine) receptor function, we performed bilateral intrastriatal (i.s.) or single intracisternal (i.c.) injections of 6-hydroxydopamine (6-OHDA) into rat pups at various postnatal ages and determined D 1 and D 2 receptor binding, adenylate cyclase activities and markers for presynaptic DA terminal density and turnover as the animals matured. All injection schedules yielded: (a) variable and partial loss of DA, (b) increased DA turnover, (c) small (15–40%) increases in D 1 receptor number but no change in affinity for antagonist ([ 3H]SCH 23390), (d) 2–3-fold increases in affinity of D 1 receptors for agonist (SKF 38393) with preserved regulation of agonist affinity by guanine nucleotide, (e) no significant changes in DA-, guanine-nucleotide-, manganese- and forskolin-stimulated AC (adenylate cyclase) activity. D 2 receptor binding was evaluated between 1 and 7 weeks of age in animals with i.s. treatment and 7 and 10 weeks of age in animals with i.c. treatment and was reduced by 40–50% with both treatment regimens. [ 3H]mazindol binding, a marker for presynaptic terminal DA transport sites, was reduced 30–40% by multiple i.s. or i.c. treatment regimens. In animals treated with one i.s. injection, [ 3H]mazindol binding was reduced 70% at 1 week of age, equal to control by 2 weeks and 14–46% greater than control between 3 and 7 weeks. We conclude that striatal D 1 receptor sites maintain their density and second messenger function independently of postsynaptic DA terminal ingrowth, whereas the development of D 2 receptor sites is sensitive to disruptions of DA terminal ingrowth.