EFFECTS OF DOPAMINE D-3 PREFERRING COMPOUNDS ON CONDITIONED PLACE PREFERENCE AND INTRACRANIAL SELF-STIMULATION IN THE RAT

Compounds showing an in vitro binding preference for the dopamine D-3 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 D-3 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 D-3 antagonist, U99194A was inactive in the ICSS model but induced significant place preference. The present results suggest that the dopamine D-3 receptor, in contrast to the D2 receptor, has an inhibitory influence on reward mechanisms.