Isolation rearing effects on probabilistic learning and cognitive flexibility in rats

Amitai, Nurith; Young, Jared W.; Higa, Kerin K.; Sharp, Richard F.; Geyer, Mark A.; Powell, Susan B.

doi:10.3758/s13415-013-0204-4

Cited by 74 publications

(57 citation statements)

References 90 publications

(142 reference statements)

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“…Changes to punishment-associative learning can be quantified similarly using the lose-shift ratio. [56][57][58][59] Thus, utilizing feedback-based decision-making tasks could illuminate reward processing capabilities in patients that may underlie negative symptoms in patients. These paradigmatic challenges to learning can readily be tested in animals.…”

Section: Integrating Reward Feedback For Decision Makingmentioning

confidence: 99%

Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia

Young

Markou

2015

SCHBUL

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Amotivation and reward-processing deficits have long been described in patients with schizophrenia and considered large contributors to patients' inability to integrate well in society. No effective treatments exist for these symptoms, partly because the neuromechanisms mediating such symptoms are poorly understood. Here, we propose a translational neuroscientific approach that can be used to assess reward/motivational deficits related to the negative symptoms of schizophrenia using behavioral paradigms that can also be conducted in experimental animals. By designing and using objective laboratory behavioral tools that are parallel in their parameters in rodents and humans, the neuromechanisms underlying behaviors with relevance to these symptoms of schizophrenia can be investigated. We describe tasks that measure the motivation of rodents to expend physical and cognitive effort to gain rewards, as well as probabilistic learning tasks that assess both reward learning and feedback-based decision making. The latter tasks are relevant because of demonstrated links of performance deficits correlating with negative symptoms in patients with schizophrenia. These tasks utilize operant techniques in order to investigate neural circuits targeting a specific domain across species. These tasks therefore enable the development of insights into altered mechanisms leading to negative symptom-relevant behaviors in patients with schizophrenia. Such findings will then enable the development of targeted treatments for these altered neuromechanisms and behaviors seen in schizophrenia.

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Section: Integrating Reward Feedback For Decision Makingmentioning

confidence: 99%

Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia

Young

Markou

2015

SCHBUL

Self Cite

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“…This task was based on a similar task developed by Bari et al (2010) and previously described (Amitai et al, 2013). Briefly, the task presented two stimuli (holes 2 and 4) wherein responses by mice in one aperture (target) were reward 80% and punished 20% of the time, whereas the contingencies were reversed for responses in the other aperture (nontarget; Figure 1d).…”

Section: Drugsmentioning

confidence: 99%

“…Magazine entries were monitored using an infrared beam mounted horizontally 5 mm from the floor and recessed 6 mm into the magazine. The control of stimuli and recording of responses were managed by a SmartCtrl Package 8-In/16-Out with additional interfacing by MED-PC for Windows (Med Associates) using custom programming (Amitai et al, 2013;Young et al, 2012Young et al, , 2013c.…”

Section: Drugsmentioning

confidence: 99%

“…RDoC domains such as cognitive control can be measured using the 5-Choice Continuous Performance Test (5C-CPT) Young et al, 2009Young et al, , 2013a, in which patients with schizophrenia (Young et al, 2013a) and bipolar mania (Young, Geyer, Minassian and Perry; unpublished observations) exhibit deficits. Positive valence, specifically the subconstruct of preference-based decision making of approach motivation, can be measured using a probabilistic learning task (Amitai et al, 2013;Bari et al, 2010), in which schizophrenia patients exhibit deficits (Armstrong et al, 2012;Gold et al, 2008;Ragland et al, 2012a;Waltz et al, 2011). The subconstruct of effort valuation can be measured using the progressive ratio breakpoint paradigm (PRBP; Bensadoun et al, 2004; that is also impaired in schizophrenia patients (Ellenbroek and Cools, 2000;Wolf et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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GlyT-1 Inhibition Attenuates Attentional But Not Learning or Motivational Deficits of the Sp4 Hypomorphic Mouse Model Relevant to Psychiatric Disorders

Young

Kamenski

Higa

et al. 2015

Neuropsychopharmacol

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Serious mental illness occurs in 25% of the general population, with many disorders being neurodevelopmental, lifelong, and debilitating. The wide variation and overlap in symptoms across disorders increases the difficulty of research and treatment development. The NIMH Research Domain of Criteria initiative aims to improve our understanding of the molecular and behavioral consequences of specific neurodevelopmental mechanisms across disorders, enabling targeted treatment development. The transcription factor Specificity Protein 4 (SP4) is important for neurodevelopment and is genetically associated with both schizophrenia and bipolar disorder. Reduced Sp4 expression in mice (hypomorphic) reproduces several characteristics of psychiatric disorders. We further tested the utility of Sp4 hypomorphic mice as a model organism relevant to psychiatric disorders by assessing cognitive control plus effort and decision-making aspects of approach motivation using cross-species-relevant tests. Sp4 hypomorphic mice exhibited impaired attention as measured by the 5-Choice Continuous Performance Test, an effect that was attenuated by glycine type-1 transporter (GlyT-1) inhibition. Hypomorphic mice also exhibited reduced motivation to work for a reward and impaired probabilistic learning. These deficits may stem from affected anticipatory reward, analogous to anhedonia in patients with schizophrenia and other psychiatric disorders. Neither positive valence deficit was attenuated by GlyT-1 treatment, suggesting that these and the attentional deficits stem from different underlying mechanisms. Given the association of SP4 gene with schizophrenia and bipolar disorder, the present studies provide support that personalized GlyT-1 inhibition may treat attentional deficits in neuropsychiatric patients with low SP4 levels.

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“…A role for serotonin was further supported by a subsequent study in mice (Ineichen et al 2012). More recently, impairments in performance in animals exposed to isolation rearing have also been reported (Amitai et al 2013). …”

Section: Reward Processing Tests In Rodent Depression Modelsmentioning

confidence: 99%

Affective Biases in Humans and Animals

Robinson

Roiser

2015

Current Topics in Behavioral Neurosciences

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Depression is one of the most common but poorly understood psychiatric conditions. Although drug treatments and psychological therapies are effective in some patients, many do not achieve full remission and some patients receive no apparent benefit. Developing new improved treatments requires a better understanding of the aetiology of symptoms and evaluation of novel therapeutic targets in pre-clinical studies. Recent developments in our understanding of the basic cognitive processes that may contribute to the development of depression and its treatment offer new opportunities for both clinical and pre-clinical research. This chapter discusses the clinical evidence supporting a cognitive neuropsychological model of depression and antidepressant efficacy, and how this information may be usefully translated to pre-clinical investigation. Studies using neuropsychological tests in depressed patients and at risk populations have revealed basic negative emotional biases and disrupted reward and punishment processing, which may also impact on non-affective cognition. These affective biases are sensitive to antidepressant treatments with early onset effects observed, suggesting an important role in recovery. This clinical work into affective biases has also facilitated back-translation to animals and the development of assays to study affective biases in rodents. These animal studies suggest that, similar to humans, rodents in putative negative affective states exhibit negative affective biases on decision-making and memory tasks. Antidepressant treatments also induce positive biases in these rodent tasks, supporting the translational validity of this approach. Although still in the early stages of development and validation, affective biases in depression have the potential to offer new insights into the clinical condition, as well as facilitating the development of more translational approaches for pre-clinical studies.

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Isolation rearing effects on probabilistic learning and cognitive flexibility in rats

Cited by 74 publications

References 90 publications

Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia

Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia

GlyT-1 Inhibition Attenuates Attentional But Not Learning or Motivational Deficits of the Sp4 Hypomorphic Mouse Model Relevant to Psychiatric Disorders

Affective Biases in Humans and Animals

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