title: A-412997, a selective dopamine D4 agonist, improves cognitive performance in rats.
abstract: The recent development of a highly selective dopamine D4 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 D4 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 D4 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.
authors.affiliation: Neuroscience Research, Abbott Laboratories, AP9A, R4N5, 100 Abbott Park Road, Abbott Park, IL 60064-6115, USA. kaitlin.e.browman@abbott.com
authors.forename: Kaitlin E
authors.initials: KE
authors.lastname: Browman
authors.forename: Peter
authors.initials: P
authors.lastname: Curzon
authors.forename: Jia Bao
authors.initials: JB
authors.lastname: Pan
authors.forename: Angela L
authors.initials: AL
authors.lastname: Molesky
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Komater
authors.forename: Michael W
authors.initials: MW
authors.lastname: Decker
authors.forename: Jorge D
authors.initials: JD
authors.lastname: Brioni
authors.forename: Robert B
authors.initials: RB
authors.lastname: Moreland
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Fox
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D003071:Cognition / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D050638:Receptors, Dopamine D4 / Q000819:agonists*
chemical_list: C506999:2-(3',4',5',6'-tetrahydro-2'H-(2,4') bipyridinyl-1'-yl)-N-m-tolyl-acetamide; D000081:Acetamides; D018491:Dopamine Agonists; D011725:Pyridines; D050638:Receptors, Dopamine D4