title: Dizocilpine (MK-801) impairs learning in the active place avoidance task but has no effect on the performance during task/context alternation.
abstract: The prevention of engram interference, pattern separation, flexibility, cognitive coordination and spatial navigation are usually studied separately at the behavioral level. Impairment in executive functions is often observed in patients suffering from schizophrenia. We have designed a protocol for assessing these functions all together as behavioral separation. This protocol is based on alternated or sequential training in two tasks testing different hippocampal functions (the Morris water maze and active place avoidance), and alternated or sequential training in two similar environments of the active place avoidance task. In Experiment 1, we tested, in adult rats, whether the performance in two different spatial tasks was affected by their order in sequential learning, or by their day-to-day alternation. In Experiment 2, rats learned to solve the active place avoidance task in two environments either alternately or sequentially. We found that rats are able to acquire both tasks and to discriminate both similar contexts without obvious problems regardless of the order or the alternation. We used two groups of rats, controls and a rat model of psychosis induced by a subchronic intraperitoneal application of 0.08mg/kg of dizocilpine (MK-801), a non-competitive antagonist of NMDA receptors. Dizocilpine had no selective effect on parallel/sequential learning of tasks/contexts. However, it caused hyperlocomotion and a significant deficit in learning in the active place avoidance task regardless of the task alternation. Cognitive coordination tested by this task is probably more sensitive to dizocilpine than spatial orientation because no hyperactivity or learning impairment was observed in the Morris water maze.
authors.affiliation: Charles University in Prague, 1st Faculty of Medicine, Katerinska 32, 12108 Prague 2, Czech Republic; Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic; National Institute of Mental Health, Topolova 748, 25067 Klecany, Czech Republic. Electronic address: Iveta.Vojtechova@fgu.cas.cz.
authors.forename: Iveta
authors.initials: I
authors.lastname: Vojtechova
authors.affiliation: Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic. Electronic address: Tomas.Petrasek@fgu.cas.cz.
authors.forename: Tomas
authors.initials: T
authors.lastname: Petrasek
authors.affiliation: Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic. Electronic address: Hana.Hatalova@fgu.cas.cz.
authors.forename: Hana
authors.initials: H
authors.lastname: Hatalova
authors.affiliation: Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic. Electronic address: Adela.Pistikova@fgu.cas.cz.
authors.forename: Adela
authors.initials: A
authors.lastname: Pistikova
authors.affiliation: Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic; National Institute of Mental Health, Topolova 748, 25067 Klecany, Czech Republic. Electronic address: Karel.Vales@fgu.cas.cz.
authors.forename: Karel
authors.initials: K
authors.lastname: Vales
authors.affiliation: Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic. Electronic address: Ales.Stuchlik@fgu.cas.cz.
authors.forename: Ales
authors.initials: A
authors.lastname: Stuchlik
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D007859:Learning Disabilities / Q000139:chemically induced* / Q000503:physiopathology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate
keywords: Active place avoidance; Context alternation; Dizocilpine; Morris water maze; Schizophrenia; Task alternation