The involvement of distraction in memory deficits induced by NMDAR antagonism: Relevance to cognitive deficits in schizophrenia

Grayson, Ben; Adamson, Lisa; Harte, Michael K.; Léger, Marianne; Marsh, Samuel; Piercy, Chloe; Neill, Joanna C.

doi:10.1016/j.bbr.2014.03.011

Cited by 18 publications

(29 citation statements)

References 24 publications

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“…We have consistently demonstrated that a low dose of risperidone improves object recognition memory (Grayson et al, 2007), reversal learning (McLean et al, 2010b) and attentional set shifting (McLean et al, 2008) deficits induced by sub-chronic PCP in female hL rats. It is important to note that the dose we use is not sufficient to block dopamine D2 receptors and is more likely to overcome the PCP deficit through other mechanisms (see Neill et al 2014 for a discussion of this topic). Even this low dose reduces object exploration and clearly has non-specific behavioural effects, as evidenced by the data shown here, however we usually observe efficacy even under these conditions in the PCP model, so are confident of its lack of efficacy in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Recognition memory in rats can be tested using the novel object recognition (NOR) task, a spontaneous and ethologically relevant paradigm based on the natural preference of rats to explore a novel object more than a familiar one after a specified time delay (Ennaceur and Delacour, 1988). Indeed, NOR has been listed by the TURNS initiative as relevant for studying visual learning and memory deficits in schizophrenia (TURNS.ucla.edu) and may be used to study cognitive deficits occurring in a range of disorders (Grayson et al, 2014). In our laboratory, we have extensively shown that sub-chronic phencyclidine (PCP) treatment impairs object recognition memory following a 1 min inter-trial interval-ITI (Damgaard et al, 2010(Damgaard et al, , 2011Grayson et al, 2007;Idris et al, 2010;McLean et al, 2009McLean et al, , 2011bSnigdha et al, 2010Snigdha et al, , 2011.…”

Section: Introductionmentioning

confidence: 99%

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Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders

McLean

Grayson

Marsh

et al. 2016

Behavioural Brain Research

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In the current study we investigated the efficacy of donepezil, risperidone and selective nicotinic α7 and α4β2 receptor agonists to reverse a delay-induced deficit in recognition memory. Adult female hooded-Lister rats received drug treatments and were tested in the novel object recognition (NOR) task following a 6 hour inter-trial interval (ITI). In all treatment groups there was no preference for the left or right identical objects in the acquisition trial. In the retention trial vehicle, risperidone (0.16mg/kg), PNU-282987, an α7 agonist (5mg/kg) and RJR-2403, an α4β2 agonist (1mg/kg) treated rats were unable to discriminate between the novel and familiar objects following a 6 hour ITI. In contrast, donepezil (1.0mg/kg), PNU-282987 (10mg/kg) and RJR-2403 (0.1mg/kg) treated rats spent significantly more time exploring the novel compared to the familiar object following the 6 hour ITI, indicative of enhanced cognitive performance (P<0.05-P<0.01). Interestingly, these compounds were efficacious when administered either before the acquisition or the retention trial of the task, suggesting an important role for nicotinic receptor subtypes in the formation and retrieval of recognition memory.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders

McLean

Grayson

Marsh

et al. 2016

Behavioural Brain Research

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“…PCP is a psychotomimetic (positive symptoms) agent, 1, 2 which is also able to induce negative 1,3 and cognitive [4][5][6][7][8] symptoms of schizophrenia and other psychiatric disorders, in humans and rodents. 9,10 In addition, it can exacerbate these symptoms in schizophrenia patients.…”

Section: Introductionmentioning

confidence: 99%

Hippocampal Proteomic and Metabonomic Abnormalities in Neurotransmission, Oxidative Stress, and Apoptotic Pathways in a Chronic Phencyclidine Rat Model

et al. 2015

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Schizophrenia is a neuropsychiatric disorder affecting 1% of the world's population. Due to a broad range of symptoms and wide heterogeneity, current therapeutic approaches in schizophrenia fail to treat all symptomatic manifestations of the disease. Therefore, new models that reproduce core pathological features of schizophrenia are needed for the elucidation of unidentified pathological disease mechanisms. Here, we employ a comprehensive global label-free liquid chromatographymass spectrometry (LC-MS) proteomic and metabonomic profiling analysis combined with targeted proteomics (selected reaction monitoring and multiplex-immunoassay) of serum and brain tissues from a chronic phencyclidine (PCP) rat model, in which NMDA-receptor hypofunction is induced through non-competitive N-methyl-D-aspartate (NMDA) antagonism. Using multiplex immunoassay, we identified serum abnormalities in cytokines (IL-5, IL-2, IL-1β) and the fibroblast-growth factor-2 levels, as peripheral biomarkers of PCP treatment. In order to find potential novel drug targets and to elucidate the pathways associated with the disease, extensive proteomic and metabonomic brain tissue profiling was employed. This revealed a more prominent effect of chronic PCP treatment on the hippocampal proteome and metabonome compared to the frontal cortex. Bioinformatic pathway analysis confirmed the abnormalities in NMDA-receptor associated pathways in both brain regions, as well as alterations in other neurotransmitter systems such as kainate, AMPA and GABAergic signalling in the hippocampus. Metabonomic profiling revealed changes in phospho-and glycolipids, which was further supported by findings of oxidative stress (superoxide dismutase) on the protein level. These molecular changes parallel findings observed in human schizophrenia. The present study could lead to increased understanding of how perturbed glutamate receptor signalling affects other relevant biological pathways in schizophrenia and therefore support drug discovery efforts for improved treatment of patients suffering from this debilitating psychiatric disorder.

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“…McLean et al 2009a;Arnt et al 2010;Damgaard et al 2010;Idris et al 2010;Damgaard et al 2011;McLean et al 2011;Snigdha et al 2011;Grayson et al 2014), in female LongEvans rats Horiguchi et al 2011a, b;, in male Lister Hooded rats(McKibben et al 2010) and in ovariectomized female Sprague-Dawley rats…”

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confidence: 98%

The subchronic phencyclidine rat model: relevance for the assessment of novel therapeutics for cognitive impairment associated with schizophrenia

et al. 2015

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The involvement of distraction in memory deficits induced by NMDAR antagonism: Relevance to cognitive deficits in schizophrenia

Cited by 18 publications

References 24 publications

Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders

Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders

Hippocampal Proteomic and Metabonomic Abnormalities in Neurotransmission, Oxidative Stress, and Apoptotic Pathways in a Chronic Phencyclidine Rat Model

The subchronic phencyclidine rat model: relevance for the assessment of novel therapeutics for cognitive impairment associated with schizophrenia

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