title: Behavioral performance altering effects of MK-801 in zebrafish (Danio rerio).
abstract: MK-801, a non-competitive NMDA-R antagonist, has been utilized in the analysis of mammalian learning and memory. The zebrafish is a novel vertebrate study species that has been proposed for the analysis of the mechanisms of learning and memory. Although learning paradigms have been developed for this species, psychopharmacological characterization of its behavioral responses is rudimentary. Before one attempts the analysis of the effects of MK-801 on learning and memory in zebrafish, one needs to know whether this drug affects motor function, perception and/or motivation, factors that may influence performance in learning tasks. Here we conduct dose response analyses investigating the effects of 0, 2, 20 and 100 μM MK-801 administered 24h or 30 min before the behavioral test, or during the test. We analyze responses in the open tank to measure motor and posture patterns, in the light dark paradigm to evaluate visual perception, and in a group preference task to attempt to quantify motivation. Our results show a significant performance alteration only in the highest (100 μM) dose groups. These fish spent more time on the bottom of their tank, showed elevated Erratic movement, increased their clockwise and counterclockwise turning frequency, and reduced the time spent near a shoal stimulus, behavioral alterations that also depended upon the timing of drug administration. Thus, using the current delivery procedures and outbred zebrafish population, the highest dose that may not lead to significant performance deficits is 20 μM, a concentration we propose to use in a future learning study in zebrafish.
authors.affiliation: Department of Psychology, University of Toronto at Mississauga, 3359 Mississauga Road, Mississauga, Ontario, Canada.
authors.forename: Margarette
authors.initials: M
authors.lastname: Sison
authors.forename: Robert
authors.initials: R
authors.lastname: Gerlai
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003623:Dark Adaptation / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D009042:Motivation / Q000187:drug effects; D012054:Reinforcement, Psychology; D012919:Social Behavior; D013997:Time Factors; D015027:Zebrafish / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate