To determine whether prolonged supersensitization of dopamine D-1 receptors could be produced during ontogeny, rats were treated daily, from birth, for 33 consecutive days with the D-1 receptor agonist, SKF 38393 HC1 (3.0 mg/kg per day i.p.). These rats were additionally treated at 3 days after birth with the neurotoxin, 6-hydroxydopamine HBr (6-OHDA; 200 μg, i.c.v., half in each lateral ventricle) or its vehicle. At 6 to 7 weeks from birth a challenge dose of SKF 38393 HCl (3.0 mg/kg i.p.) increased stereotypy scores for a number of behaviors in 6-OHDA-lesioned rats that were treated repeatedly during ontogeny with SKF 38393. These accentuated behaviors included licking, grooming, taffy pulling, jumping, paw treading and locomotion. Although the findings demonstrate an increased sensitivity of D-1 receptors to an agonist, there was no change in the Bmax or Kd for D-1 receptors in the striatum. In rats that were treated during postnatal development with SKF 38393, but not lesioned with 6-OHDA, SKF 38393-induced stereotyped behaviors were not substantially different from control. The neonatally primed rat model may be useful for probing mechanisms of receptor supersensitivity.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) destroys dopamine-containing nigrostriatal neurons and increases the apparent Bmax of both D1 and D2 binding sites in the striatum. However, the changes of Bmax occur at different intervals after the lesion. Up-regulation of D2 sites becomes evident about 3 weeks after the lesion and lasts for about 3 months. In contrast, about 3 months are required for the up-regulation of D1 sites and increased binding is still evident after 5 months.