Supersensitivity to a D-1 dopamine receptor agonist and subsensitivity to a D-2 receptor agonist following chronic D-1 receptor blockade

The effect of chronic D-1 dopamine (DA) receptor blockade on D-1 DA receptors and DA-mediated behaviors was studied in rats with unilateral, quinolinic acid-induced striatal lesions. Administration of the selective D-1 antagonist SCH 23390 for 15 days increased D-1 receptor numbers in the unlesioned striatum as indicated by [125I]SCH 23982 binding; ipsilateral turning initiated by the D-2 receptor agonist LY 171555 decreased, while grooming produced by the D-1 receptor agonist SKF 38393 intensified. There was, however, no change in the ability of the D-1 agonist to potentiate D-2 agonist-mediated rotation. The observed behavioral subsensitivity in response to a D-2 agonist may reflect D-1 receptor upregulation and the consequent imbalance of D-1/D-2 receptor interactions in the striatum where these two receptor subtypes appear to play opposite functional roles; potentiation of grooming, primarily a D-1 receptor-mediated behavior, may also reflect the increase in D-1 receptor numbers.