A-412997, a selective dopamine D(4) agonist,
improves cognitive performance in rats

Browman KE, Curzon P, Pan JB, Molesky AL, Komater VA,
Decker MW, Brioni JD, Moreland RB, Fox GB.
Neuroscience Research, Abbott Laboratories,
AP9A, R4N5, 100 Abbott Park Road,
Abbott Park, IL 60064-6115, United States.
Pharmacol Biochem Behav. 2005 Sep 7


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 tool 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 D(4) receptor subtype in cognition.

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