E. Acquas et G. Dichiara, D1 RECEPTOR BLOCKADE STEREOSPECIFICALLY IMPAIRS THE ACQUISITION OF DRUG-CONDITIONED PLACE PREFERENCE AND PLACE AVERSION, Behavioural pharmacology, 5(6), 1994, pp. 555-569
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 i
n a place-conditioning paradigm. Drugs tested were two potent D1 recep
tor antagonists, SCH 23390 and SCH 39166, that differ in the poor affi
nity of the latter for 5-HT2 receptors, and SCH 23388, the inactive en
antiomer 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 pl
ace aversion. Higher doses of the D1 antagonists or pairing for 60 min
with one compartment failed to elicit place aversion. SCH 39166 (50 m
u g/kg s,c.) paired with both compartments completely prevented the pl
ace-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 preferenc
e. The D1 antagonists also impaired the acquisition of morphine-induce
d place preference and lithium-induced place aversion but only at high
er 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 motiva
tion: 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 (incenti
ve learning).