title: Effects of the cognition impairer MK-801 on learning and memory in mice and rats.
abstract: There is a great need for relevant animal models for investigating the effects of putative pro-cognitive compounds. Compounds that impair learning and/or memory processes without inducing adverse side effects are cognition impairers. Rats and mice with cognitive deficits induced by the prototypical N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 may provide a relevant animal model based on the mechanistic approach of blocking NMDA/glutamatergic signaling. Unfortunately, the dose range over which MK-801 induces cognitive impairment without causing sensory, locomotor, or toxicological side effects is small. We provide an overview of the effects of MK-801 in different cognitive tasks and assessed whether MK-801 reliably affects the cognitive performance of mice or rats in the spatial Morris task, T-maze alternation tasks, and non-spatial passive avoidance, social, and object recognition tasks. MK-801 disrupted or retarded memory acquisition in all tasks. The Morris task, once acquired, was insensitive to MK-801 at a dose up to 0.1 mg kg(-1) body weight. Retention deficits in the passive avoidance tests were not likely to be due to MK-801-induced changes in shock sensitivity, as measured by a shock threshold test. On the basis of published evidence and the present findings, we conclude that MK-801, administered s.c. or i.p. into rodents in doses up to 0.1 mg kg(-1), appears to fulfill the criteria of our definition of a cognition impairer in rodents, without causing sensorimotor impairments and/or signs of intoxication. In addition, MK-801-treated rodents appear to fulfill the criteria of a valid animal model of cognitive dysfunctions, with robust effects across species, housing conditions, and testing paradigms.
authors.affiliation: University Utrecht, Faculty of Veterinary Medicine, Department of Farm Animal Health, Program Emotion & Cognition, P.O. Box 80151, 3508 TD Utrecht, The Netherlands. f.j.vanderstaay@uu.nl
authors.forename: F Josef
authors.initials: FJ
authors.lastname: van der Staay
authors.forename: Kris
authors.initials: K
authors.lastname: Rutten
authors.forename: Christina
authors.initials: C
authors.lastname: Erb
authors.forename: Arjan
authors.initials: A
authors.lastname: Blokland
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001288:Attention / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects*; D012684:Sensory Thresholds / Q000187:drug effects
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate