Blockade of dopamine D(3) receptors in frontal cortex, but not in sub-cortical structures, enhances social recognition in rats: similar actions of D(1) receptor agonists, but not of D(2) antagonists.

Though D(3) receptor antagonists can enhance cognitive function, their sites of action remain unexplored. This issue was addressed employing a model of social recognition in rats, and the actions of D(3) antagonists were compared to D(1) agonists that likewise possess pro-cognitive properties. Infusion of the highly selective D(3) antagonists, S33084 and SB277,011 (0.04-2.5 microg/side), into the frontal cortex (FCX) dose-dependently reversed the deficit in recognition induced by a delay. By contrast, the preferential D(2) antagonist, L741,626 (0.63-5.0) had no effect. The action of S33084 was regionally specific inasmuch as its injection into the nucleus accumbens or striatum was ineffective. A similar increase of recognition was obtained upon injection of the D(1) agonist, SKF81297 (0.04-0.63), into the FCX though it was also active (0.63) in the nucleus accumbens. These data suggest that D(3) receptors modulating social recognition are localized in FCX, and underpin their pertinence as targets for antipsychotic agents.