Evidence for a role for dopamine D3 receptors in the effects of dopamine agonists on operant behaviour in rats.

The results of this study are consistent with the view that D3 DA receptors may play an important role in mediating the behavioural effects of DA agonists and that these receptors have a presynaptic location.

Abstract

Several dopamine (DA) agonists have been reported to show some D3 versus D2 selectivity but the extent of this selectivity depends on experimental conditions, and the behavioural effects of these compounds seem to differ little from those of non-selective agonists such as apomorphine. However, some recent studies have reported stronger correlations between several behavioural responses and D3 affinities than between the same responses and affinities for D2 receptors. In the present study rats were trained to lever press for food on a fixed-ratio (FR10) schedule during daily 15min sessions. The DA agonists apomorphine; quinelorane; quinpirole; 7-hydroxy-2-(di-n-propylamino)-tetralin [(+/-)7-OH-DPAT]; (+)-(4aR, 10bR)-4-propyl-3, 4,4a, 10b-tetrahydro-2H,5H-1-benzopyrano [4,3-b], 4(oxazin-9-ol); bromocriptine; and (3-hydroxyphenyl)-N-propylpiperidine produced dose-related decreases in these response rates. The potencies of these compounds correlated significantly with their published potencies to produce a functional D3 but not a functional D2 response (stimulation of mitogenesis in transfected cells). The rate-decreasing effects of 7-OH-DPAT were antagonised by the benzamide antipsychotic agent amisulpride, at low doses (1 and 3mg/kg) which have been shown to exert preferential activity at presynaptic DA receptors. 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 agonists and that these receptors have a presynaptic location.