Three groups of rats (n = 8/group) were trained in a two-lever, food-reinforced drug discrimination paradigm to discriminate the D1 agonist SKF 38393 (SKF; 8.0 mg/kg, IP) from saline. After acquisition of the discrimination, the dose-response function for SKF (2.0-16 mg/kg, IP) was determined using a cumulative dosing procedure. In one group, the SKF dose-response function was redetermined 1 week after a regimen of 0.25 mg/kg of the D1 antagonist SCH 23390 (SCH), IP, once/day for 10 days, again 1 week after a second regimen of 0.5 mg/kg SCH, IP, twice/day for 10 days, and a third time after a regimen of 1.0 mg/kg SCH, IP, twice/day for 21 days. SKF dose-response functions were redetermined in a group of control rats after identical injection regimens of saline. In the third group of rats, SKF dose-response functions were redetermined 24 h after an injection of N-ethoxycarboxyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (irreversible antagonist) vehicle; again 24 h after an injection of 3.0 mg/kg; again 48 h after 6.0 mg/kg EEDQ; and finally 48 h after two consecutive daily injections of 6.0 mg/kg EEDQ (12 mg/kg total). The dose-response function for the percentage of responses that occurred on the SKF lever (%DL) shifted significantly to the left following the second regimen of SCH; there was no further shift after the third regimen. The effects of SKF on response rate were unchanged by SCH administration. Repeated administration of saline did not alter the SKF dose-response function for %DL or response rate.(ABSTRACT TRUNCATED AT 250 WORDS)