Behavioral differentiation of the stimulus properties of a dopaminergic D1 agonist from a D2 agonist

This study examined the hypothesis that the stimulus properties of a dopaminergic D1 agonist should be functionally discriminable from those of a D2 agonist. Rats were trained in a two-lever food-reinforced drug discrimination paradigm to discriminate either the D1 agonist SKF 38393 from apomorphine (SKF/APO), SKF from saline (SKF/SAL) or apomorphine from saline (APO/SAL), at an APO dose previously established to have D2-mediated stimulus properties. Results showed the SKF/APO discrimination to be readily acquired. The SKF cue showed similar stimulus properties under both the SKF/APO and SKF/SAL training conditions which were mediated by the D1 receptor: the SKF response was blocked by the D1 antagonist SCH 23390, but not by the D2 antagonist haloperidol. Run length data suggested a graded rather than quantal effect of SKF dose on responding during SKF generalization tests. In APO/SAL-trained animals, the APO cue was D2 mediated; responding was blocked by haloperidol, but not by SCH 23390 and APO responding generalized to the selective D2 agonist LY 171555 (quinpirole), but not to SKF. In the SKF/APO condition, APO responding did not decrease with APO dose, nor were antagonists effective in blocking responding, reflecting the lack of an alternative no-drug response option. Higher doses of APO appear to have D1 properties; doses above the training dose engendered SKF responding in both the SKF/SAL and SKF/APO groups, a response which could be blocked by the D1 antagonist SCH 23390, but not by the D2 antagonist, haloperidol. In all three training conditions, generalization test outcomes could be influenced by the conditions of the previous test session.(ABSTRACT TRUNCATED AT 250 WORDS)