title: Effects of the GluN2B-NMDA receptor antagonist Ro 25-6981 on two types of behavioral flexibility in rats.
abstract: Recent evidence has implicated N-methyl-d-aspartate receptors (NMDARs) in several aspects of learning and behavioral flexibility in rodents. Here, we examined the effects of treatment with Ro 25-6981, a selective antagonist of NMDARs containing GluN2B subunits, on two types of behavioral flexibility in rats, spatial reversal learning and set-shifting (spatial vs. motor strategy). To examine spatial reversal learning, rats were trained to swim to a hidden platform in a water maze over four days. On the following day, the platform was moved to a new location in the maze. Administration of Ro 25-6981 (10mg/kg) selectively impaired the early phase of reversal learning, but all rats learned to navigate to the new platform location over 12 trials. To examine set-shifting, independent groups of rats were trained to either swim to a fixed location (spatial strategy) or use a motor response (e.g., "turn left"; motor strategy) to find a hidden escape platform in a cross-shaped water maze apparatus; after task acquisition, rats were trained on the second, novel strategy (set-shift) following treatment with either Ro 25-6981 (10mg/kg) or saline. Administration of Ro 25-6981 had no effect on the ability of rats to perform the set-shift and use the new strategy to locate the escape platform. These results suggest that, in rats, spatial reversal learning, but not set-shifting, is sensitive to Ro-25-6981 treatment. Thus, NMDARs-GluN2B signaling may play a selective role in some forms of behavioral plasticity, particularly for situations involving the updating of information in the spatial domain.
authors.affiliation: Department of Psychology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Emma
authors.initials: E
authors.lastname: Clark
authors.affiliation: Department of Psychology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Kristen
authors.initials: K
authors.lastname: Antoniak
authors.affiliation: Department of Psychology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Alyssandra
authors.initials: A
authors.lastname: Feniquito
authors.affiliation: Department of Psychology, Queen's University, Kingston, Ontario K7L 3N6, Canada; Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada. Electronic address: dringenb@queensu.ca.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Dringenberg
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001288:Attention / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012193:Reversal Learning / Q000187:drug effects*; D013037:Spatial Behavior / Q000187:drug effects*
chemical_list: C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981
keywords: GluN2B subunit; Motor strategy; N-methyl-d-aspartate receptors; Rat; Reversal learning; Set-shifting; Spatial strategy; Water maze