Behavioral effects of chronic exposure to selective D-1 and D-2 dopamine receptor agonists

Abstract

Chronic treatment with the selective D-1 agonist SKF 38393 induced behavioral supersensitivity (increased stereotypy and decreased locomotor activity) in response to apomorphine. In contrast, chronic treatment with the selective D-2 agonist LY 171555 resulted in a subsensitive behavioral response to apomorphine challenge. Chronic treatment with the combination of these drugs augmented apomorphine-induced stereotypic behaviors, but these were different in nature from those observed in animals treated with SKF 38393 alone. Chronic SKF 38393 treatment resulted in an enhanced behavioral response to SKF 38393 itself. Behavioral response to LY 171555 was affected only by chronic treatment with the combination of selective agonists. These results suggest that chronic D-1 receptor stimulation may be necessary and sufficient for the development of dopamine agonist-induced behavioral sensitization in the intact rat; the mechanism may involve increased sensitivity of D-1 receptor-associated mechanisms. Chronic D-2 receptor stimulation appears to have the opposite effect. These results also provide evidence that a synergistic interaction between receptor subtypes may underlie certain behavioral effects of chronic agonist exposure.