The involvement of dopamine D2 receptors, but not D3 or D4 receptors, in the rewarding effect of brain stimulation in the rat

To identify the subtype of dopamine receptors critically involved in the rewarding effect of brain stimulation, four dopamine antagonists were intracranially injected in 25 rats. The importance of dopamine D1 receptors had been demonstrated previously by using SCH 23390, a highly selective D1 antagonist. Rats were implanted with electrodes into the medial forebrain bundle and cannulae into either one of the following structures: the nucleus accumbens, the vicinity of the islands of Calleja, or the ventral tegmental area, all ipsilateral to the electrodes. The animals were trained to press a bar for electrical stimulation, and the frequency-response functions were plotted before and after injection of each dopamine antagonist through the cannulae. Raclopride and haloperidol, which have high affinities for D2 receptors, reduced the rewarding effect after injection into any one of the three cannula sites. Neither (+)-UH232, a selective D3 antagonist, nor clozapine, a D4 antagonist, influenced the rewarding effect. The results suggest that dopamine D2, but not D3 or D4, receptors are critically involved in producing the rewarding effect of brain stimulation. (C) 1997 Elsevier Science B.V.