EVIDENCE FOR A ROLE FOR DOPAMINE D3 RECEPTORS IN THE EFFECTS OF DOPAMINE AGONISTS ON OPERANT-BEHAVIOR IN RATS

Several dopamine (DA) agonists have been reported to show some D3 vers us D2 selectivity but the extent of this selectivity depends on experi mental conditions, and the behavioural effects of these compounds seem to differ little from those of nonselective agonists such as apomorph ine. However, some recent studies have reported stronger correlations between several behavioural responses and D3 affinities than between t he same responses and affinities for D2 receptors. In the present stud y rats were trained to lever press for food on a fixed-ratio (FR10) sc hedule during daily 15 min sessions. The DA agonists apomorphine; quin elorane; quinpirole; 7-hydroxy-2-(di-n-propylamino)-tetralin [(+/-)7-O H-DPAT]; (+)-(4aR, 10bR)-4-propyl-3,4,4a, 10b-tetrahydro-2H,5H-1-benzo pyrano [4,3-b], 4(oxazin-9-ol); bromocriptine; and (3-hydroxyphenyl)-N -propylpiperidine produced dose-related decreases in these response ra tes. The potencies of these compounds correlated significantly with th eir published potencies to produce a functional D3 but not a functiona l D2 response (stimulation of mitogenesis in transfected cells). The r ate-decreasing effects of 7-OH-DPAT were antagonised by the benzamide antipsychotic agent amisulpride, at low doses (1 and 3 mg/kg) which ha ve been shown to exert preferential activity at presynaptic DA recepto rs. Haloperidol and remoxipride produced only small antagonist effects . These results are consistent with the view that D3 DA receptors may play an important role in mediating the behavioural effects of DA agon ists and that these receptors have a presynaptic location.