Two learning tasks provide evidence for disrupted behavioural flexibility in an animal model of schizophrenia-like behaviour induced by acute MK-801: A dose–response study

Lobellová, Veronika; Entlerova, Marie; Svojanovska, Barbora; Hatalova, Hana; Prokopova, Iva; Petrásek, Tomáš; Valeš, Karel; Kubík, Štěpán; Fajnerová, Iveta; Stuchlı́k, Aleš

doi:10.1016/j.bbr.2013.03.006

Cited by 42 publications

(42 citation statements)

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“…Such settings could be a source of skill learning effect that could explain the lack of between-group differences observed in the navigation accuracy. Nevertheless, the low sensitivity of the reversal protocol toward the cognitive deficit in schizophrenia is in accordance with the animal studies that failed to find group differences after application of lower doses of MK-801 (Watson and Stanton, 2009; Lobellova et al, 2013). Interestingly, similar reversal protocol applied in the avoidance task on the rotating arena showed that the pre-training of animals in the task (as in our RM session) can lead to lack of group differences after application of MK-801 (Zemanova et al, 2013).…”

Section: Discussionsupporting

confidence: 71%

“…Measurable impairment of visuo-spatial abilities in MWM has already been demonstrated in several animal models of schizophrenia (see review; Bubenikova-Valesova et al, 2008). Several animal studies including the work of our group confirmed that the rodent model of schizophrenia based on administration of MK-801 (dizocilpine, a non-competitive NMDA glutamate receptor antagonist) leads to decreased cognitive functioning in rats, resulting in compromised performance in all variants (reference, reversal, and working memory protocol) of the MWM task (Stuchlik et al, 2004; Vales et al, 2006; van der Staay et al, 2011; Lobellova et al, 2013). …”

Section: Introductionmentioning

confidence: 70%

“…The goal was moved after each 3 trials (see Figure 3B). It was based on a modified reversal protocol of the MWM, in which the goal position is changed over the days used to test mental flexibility (Lipp et al, 1998; Vorhees and Williams, 2006; Garthe et al, 2009; Lobellova et al, 2013) and/or working memory (Morris et al, 1986). Unlike in rats, the change in goal position was separated not by days of testing but by an announcement to the subjects, in order to test their memory for spatial sequence (ABC) in the subsequent phases.…”

Section: Methodsmentioning

confidence: 99%

“…The probe trials, with a removed hidden platform adopted from the animal studies, provide an important demonstration of memory processes in terms of spatial bias (Morris et al, 1982, 1990; Sutherland et al, 1983; Whishaw, 1991). In rats probe trials are usually conducted in the reference memory protocols, but sometimes after reversal condition as well (Lobellova et al, 2013). …”

Section: Methodsmentioning

confidence: 99%

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A virtual reality task based on animal research â€“ spatial learning and memory in patients after the first episode of schizophrenia

Fajnerová

Rodríguez²,

Levčík

et al. 2014

Front. Behav. Neurosci.

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Objectives: Cognitive deficit is considered to be a characteristic feature of schizophrenia disorder. A similar cognitive dysfunction was demonstrated in animal models of schizophrenia. However, the poor comparability of methods used to assess cognition in animals and humans could be responsible for low predictive validity of current animal models. In order to assess spatial abilities in schizophrenia and compare our results with the data obtained in animal models, we designed a virtual analog of the Morris water maze (MWM), the virtual Four Goals Navigation (vFGN) task.Methods: Twenty-nine patients after the first psychotic episode with schizophrenia symptoms and a matched group of healthy volunteers performed the vFGN task. They were required to find and remember four hidden goal positions in an enclosed virtual arena. The task consisted of two parts. The Reference memory (RM) session with a stable goal position was designed to test spatial learning. The Delayed-matching-to-place (DMP) session presented a modified working memory protocol designed to test the ability to remember a sequence of three hidden goal positions.Results: Data obtained in the RM session show impaired spatial learning in schizophrenia patients compared to the healthy controls in pointing and navigation accuracy. The DMP session showed impaired spatial memory in schizophrenia during the recall of spatial sequence and a similar deficit in spatial bias in the probe trials. The pointing accuracy and the quadrant preference showed higher sensitivity toward the cognitive deficit than the navigation accuracy. Direct navigation to the goal was affected by sex and age of the tested subjects. The age affected spatial performance only in healthy controls.Conclusions: Despite some limitations of the study, our results correspond well with the previous studies in animal models of schizophrenia and support the decline of spatial cognition in schizophrenia, indicating the usefulness of the vFGN task in comparative research.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 70%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A virtual reality task based on animal research â€“ spatial learning and memory in patients after the first episode of schizophrenia

Fajnerová

Rodríguez²,

Levčík

et al. 2014

Front. Behav. Neurosci.

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“…The hypofunction of glutamatergic receptors is the pathophysiology of schizophrenia of the glutamatergic hypothesis, and the N-methyl-d-aspartate receptor (NMDAR) antagonists, such as dizocilpine (MK-801), phencyclidine, and ketamine, produce schizophrenia-like behavior and cognitive deficits (Gaspar, Bustamante, Silva, & Aboitiz, 2009;Lobellova et al, 2013;Meltzer et al, 2013). Acute treatment with MK-801 is extensively utilized to establish animal model of cognitive impairment, such as spatial learning and memory.…”

Section: Introductionmentioning

confidence: 99%

Effects of haloperidol, olanzapine, ziprasidone, and PHA‐543613 on spatial learning and memory in the Morris water maze test in naïve and MK‐801‐treated mice

et al. 2017

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Introduction Cognitive impairment is the core symptom of schizophrenia, significantly impacting the functional outcome. Improvement of cognitive function has been an important aspect of the treatment of schizophrenia. Therefore, this study is to demonstrate the effects of first‐generation antipsychotic haloperidol, second‐generation antipsychotic olanzapine and ziprasidone, and alpha‐7 nicotinic acetylcholine receptor agonist PHA ‐543613 on spatial learning and memory. Material and Methods C57 BL /6 mice received intraperitoneal injections of haloperidol (2 mg/kg), olanzapine (2.5 mg/kg), ziprasidone (2 mg/kg), and PHA ‐543613 (1 mg/kg), and cognitive dysfunctions were induced by MK ‐801 (0.1 mg/kg). Morris water maze was used for investigating the effects of all agents. Results Mk‐801 significantly increased the mean escape latency to the platform and decreased the number of platform area crossings. Ziprasidone had no effect on the mean escape latency to platform and the number of platform area crossings in naïve mice, but haloperidol, olanzapine, and PHA ‐543613 did not. Haloperidol and olanzapine significantly increased the mean escape latency to platform and decreased the number of platform area crossings, while ziprasidone and PHA ‐543613 did not. All the agents had no effect on swimming speed. Conclusions Ziprasidone and alpha‐7 nicotinic acetylcholine receptor agonist PHA ‐543613 might be helpful in the treatment of CIAS .

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Neuropathological Background of MK-801 for Inducing Murine Model of Schizophrenia

Murueta‐Goyena

Odrioizola

Gargiulo

et al. 2017

Psychiatry and Neuroscience Update - Vol. II

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Two learning tasks provide evidence for disrupted behavioural flexibility in an animal model of schizophrenia-like behaviour induced by acute MK-801: A dose–response study

Cited by 42 publications

References 42 publications

A virtual reality task based on animal research â€“ spatial learning and memory in patients after the first episode of schizophrenia

A virtual reality task based on animal research â€“ spatial learning and memory in patients after the first episode of schizophrenia

Effects of haloperidol, olanzapine, ziprasidone, and PHA‐543613 on spatial learning and memory in the Morris water maze test in naïve and MK‐801‐treated mice

Neuropathological Background of MK-801 for Inducing Murine Model of Schizophrenia

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