A-412997, a selective dopamine D4 agonist, improves cognitive performance in rats

The recent development of a highly selective dopamine D-4 receptor agonist, A-412997 (2-(3',4',5',6'-tetrahydro-2'H-[2,4'] bipyridinyl-1'yl)-N-m-tolyl-acetamide), has provided a pharmacological too] with which to conduct systematic investigations into the putative role for dopamine D-4 receptors in the central nervous system. These present studies evaluated the potential cognitive enhancing properties of A-412997 in rat models of ADHD (5-trial repeated acquisition inhibitory avoidance in Spontaneous Hypertensive Rat pups) and short-term memory (Social Recognition), in comparison with the less selective dopamine D-4 receptor agonists PD168077 and CP226269. A-412997 showed significant dose-dependent efficacy in both models. PD168077 repeatedly improved acquisition in the 5-trial inhibitory avoidance model but failed to reach significance at any dose tested, although significantly improved social recognition was observed (albeit less potent than A-412997). CP226269 showed a significant enhancement in the 5-trial inhibitory avoidance model. These results support a role for the dopamine D4 receptor subtype in cognition. (c) 2005 Elsevier Inc. All rights reserved.