Unilateral inactivation of dopamine receptors after intrastriatal injection of N-ethoxy-carbonyl-2- ethoxy-1,2-dihydroquinoline (EEDQ): A novel rotational model to investigate dopamine receptor interactions

Abstract

The interaction between D1 and D2 dopamine (DA) receptors was investigated in a novel rotational model. Rats were unilaterally injected into the striatum with the irreversible DA receptor blocker N-ethoxycarbonyl- 2-ethoxy-1,2-dihydroquinoline (EEDQ). This treatment induced a marked decrease in the density of D1 (−48%) and D2 (−45%) DA receptors available for binding to 3H-SCH 23390 and 3H-spiperone, respectively. Under these experimental conditions, the effect of DA receptor agonists were predominant on the intact side and resulted in rotations ipsilateral to the injected side. The effects of different agonists and antagonists for D1 and D2 DA receptors were evaluated 24 hr after EEDQ administration. The D2 agonist LY 171555 induced ipsilateral rotations in a dose-dependent manner (0.1–10.0 mg/kg, IP) in rats treated intrastriatally with EEDQ. In contrast, the D1 agonist SKF 38393 (1–20 mg/kg, IP) was unable to elicit circling behavior per se. However, SKF 38393 increased the number of rotations caused by LY 171555. The circling behavior induced by LY 171555 was blocked by the D2 antagonists (−)sulpiride and raclopride and by the D1 antagonist SCH 23390. Moreover, the inhibition of circling behavior induced by SCH 23390 was reversed by SKF 38393 in a dose-dependent manner. LY 171555 (1 mg/kg, IP) was unable to induce rotations in EEDQ-treated rats following DA depletion by α-methyl-p-tyrosine, whilst the combined administration of LY 171555 (1 mg/kg, IP) and SKF 38393 (10 mg/kg, IP) elicited intense circling behavior in DA depleted rats. Finally, the effect of LY 171555 plus SKF 38393 was completely antagonized by SCH 23390 (0.1 mg/kg, SC). These results indicate that the endogenous DAergic tone on D1 DA receptors plays a permissive role for the expression of the motor effects mediated via the stimulation of striatal D2 DA receptors.