D1 RECEPTOR BLOCKADE STEREOSPECIFICALLY IMPAIRS THE ACQUISITION OF DRUG-CONDITIONED PLACE PREFERENCE AND PLACE AVERSION

The motivational effects of dopamine (DA) D1 receptor blockade and its influence on the motivational effects of amphetamine (1.0 mg/kg s.c.), morphine (1.0 mg/kg s.c.) and lithium (40 mg/kg s.c.) were studied in a place-conditioning paradigm. Drugs tested were two potent D1 receptor antagonists, SCH 23390 and SCH 39166, that differ in the poor affinity of the latter for 5-HT2 receptors, and SCH 23388, the inactive enantiomer of SCH 23390. SCH 23390 and SCH 39166, at low doses (12.5 and 25 mu g/kg s.c.), paired for 30 min with one compartment, elicited place aversion. Higher doses of the D1 antagonists or pairing for 60 min with one compartment failed to elicit place aversion. SCH 39166 (50 mu g/kg s,c.) paired with both compartments completely prevented the place-aversion elicited by SCH 23390 (12.5 mu g/kg s.c.). SCH 23390 and SCH 39166 at low doses (12.5 and 25 mu g/kg s.c. respectively), paired with both compartments, abolished amphetamine induced place preference. The D1 antagonists also impaired the acquisition of morphine-induced place preference and lithium-induced place aversion but only at higher doses (50 and 100 mu g/kg s.c.). These effects were stereospecific as the inactive enantiomer SCH 23388, up to a dose of 500 mu g/kg s.c., failed to impair the acquisition of amphetamine and morphine-induced place preference. It is concluded that DA plays a dual role in motivation: one role is that of assigning motivational valence to stimuli in relation to changes in DA transmission; another role of DA relates to the learning process involved in the acquisition of positive as well as negative incentive properties by otherwise neutral stimuli (incentive learning).