D1 receptor blockade stereospecifically impairs the acquisition of drug-conditioned place preference and place aversion

Abstract

The motivational effects of dopamine (DA) D1 receptor blockade and its influence on the motivational effects of amphetamine (1.0mg/kg s.c.), morphine (1.0mg/kg s.c.) and lithium (40mg/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-HT(2) receptors, and SCH 23388, the inactive enantiomer of SCH 23390. SCH 23390 and SCH 39166, at low doses (12.5 and 25µg/kg s.c.), paired for 30min with one compartment, elicited place aversion. Higher doses of the D1 antagonists or pairing for 60min with one compartment failed to elicit place aversion. SCH 39166 (50µg/kg s.c.) paired with both compartments completely prevented the place-aversion elicited by SCH 23390 (12.5µg/kg s.c.). SCH 23390 and SCH 39166 at low doses (12.5 and 25µg/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 100µg/kg s.c.). These effects were stereospecific as the inactive enantiomer SCH 23388, up to a dose of 500µg/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).