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 mu g/side), into the frontat cortex (FCX) dose-dependentty 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. (C) 2008 Published by Elsevier B.V.