Single apomorphine pretreatment results in a rapid decline in high-affinity dopamine binding to the striatal dopamine...

The formation of a ternary complex of agonist, receptor, and G-protein precedes inhibition of adenylate cyclase and is associated with high-affinity agonist binding. The present experiment was conducted to determine if a single direct dopamine (DA) agonist, apomorphine (APO), pretreatment could produce a rapid uncoupling of the striatal DA D-2 receptor from its G-proteins. APO (30 mg/kg, i.p.) and saline were administered once, with killing 60 or 90 min following the APO or vehicle treatment. APO pretreatment resulted in a reduction in the high-affinity binding of DA to the striatal DA D-2 receptor without altering total agonist binding. The total density of antagonist-defined D-2 receptors (Bmax) was not altered by the treatment. The present results represent, to our knowledge, the first demonstration of changes in high-affinity agonist binding to the DA D-2 receptor following a single in vivo pretreatment of a direct DA agonist.