Ontogenetic quinpirole treatments fail to prime for D2 agonist-enhancement of locomotor activity in 6-hydroxydopamine-lesioned rats

Repeated treatments with a dopamine (DA) D-2 receptor agonist results in the induction of DA D-2 receptor supersensitivity, as evidenced by enhanced behavioral responses to subsequent D-2 agonist treatments - a phenomenon known as priming of receptors. Priming of D-2 receptors has been well-studied in otherwise intact (non-lesioned) rats. In contrast to D2 priming, repeated treatments with a DA D-1 agonist are unable to prime D-1 receptors unless nigrostriatal DA fibers are largely destroyed in early postnatal ontogeny. In order to determine if D-2 receptors could be primed in rats in which nigrostriatal DA fibers were largely destroyed in early postnatal ontogeny, rats were (a) lesioned at 3 days after birth with 6-hydroxydopamine (67 mug in each lateral ventricle; desipramine, 20 mg/kg IP, 1 h; 6-OHDA), (b) treated daily for the first 28 days after birth with the D-2 agonist quinpirole HCl (3.0 mg/kg IP), and (c) observed in adulthood for both quinpirole-induced and SKF 38393- (D-1 agonist-) induced locomotor activity and stereotyped activities. In 6-OHDA-lesioned rats in which endogenous striatal DA was reduced by 99%, quinpirole did not produce enhanced locomotor or stereotyped activities. However, SKF 38393 produced increased locomotor and stereotyped activities even after the first dose of SKF 38393. These findings demonstrate that D-2 receptors are not primed by ontogenetic quinpirole treatments of neonatally 6-OHDA-lesioned rats, although D-2 agonist treatments do at least partially prime D-1 receptors in 6-OHDA-lesioned rats.