Compounds showing an in vitro binding preference for the dopamine D3 receptor were tested in two models designed to assess positive reinforcement in the rat: intracranial self-stimulation (ICSS) and conditioned place preference (CPP). R-(+)-7-OH-DPAT, a D3 preferring agonist, inhibited ICSS behaviour over a wide dose range. At higher doses, a facilitation of ICSS was seen. In the CPP model, 7-OH-DPAT was inactive except at the highest dose where a significant change in preference was seen. A dose of R-(+)-7-OH-DPAT, that significantly inhibited ICSS behaviour, was combined with a dose of d-amphetamine, that significantly facilitated ICSS behaviour. Surprisingly, this resulted in a significant synergistic facilitation of the amphetamine response. The putative D3 antagonist, U99194A was inactive in the ICSS model but induced significant place preference. The present results suggest that the dopamine D3 receptor, in contrast to the D2 receptor, has an inhibitory influence on reward mechanisms.

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