Dopaminergic control of cognitive flexibility in humans and animals

Klanker, Marianne; Feenstra, Matthijs G.P.; Denys, Damiaan

doi:10.3389/fnins.2013.00201

Cited by 188 publications

(188 citation statements)

References 293 publications

Supporting

Mentioning

182

Contrasting

Order By: Relevance

“…Flexibility refers to the ability to revise a course of action in the face of unpredicted difficulties or obstacles, change one's own ideas in the light of new evidence, and adapt to changes that different life epochs or contingent situations may require. Lack of flexibility may result in great distress for a person undergoing sudden and/or important life changes, and is an important aspect of several psychiatric disorders, such as obsessive personality or delusional disorder (26).…”

Section: Toward a New Definition Of Mental Healthmentioning

confidence: 99%

A proposed new definition of mental health

Galderisi¹,

Heinz²,

Kastrup³

et al. 2017

Psychiatr Pol

View full text Add to dashboard Cite

show abstract

Section: Toward a New Definition Of Mental Healthmentioning

confidence: 99%

A proposed new definition of mental health

Galderisi¹,

Heinz²,

Kastrup³

et al. 2017

Psychiatr Pol

View full text Add to dashboard Cite

show abstract

“…Visual discrimination learning requires perceptual learning and memory processing [1,2], while reversal learning assesses behavioral flexibility of learning [3,4]. Abnormalities in visual discrimination learning have been shown in patients with depression, autism, and Alzheimer's disease, while impairments of reversal learning have been shown in patients with schizophrenia and Alzheimer's disease [5,6,7,8,9].…”

Section: Introductionmentioning

confidence: 99%

Dopamine D2L Receptor Is Required for Visual Discrimination and Reversal Learning

et al. 2016

View full text Add to dashboard Cite

The corticostriatothalamic circuit regulates learning behaviors via dopamine neurotransmission. D2 long (D2L) receptors are an isoform of dopamine D2 receptors (D2Rs) and may act mainly at postsynaptic sites. It is well known that D2Rs influence high brain functions, but the roles of individual D2R isoforms are still unclear. To assess the influence of D2L receptors in visual discrimination learning, we performed visual discrimination and reversal tasks with D2L knockout mice using a touchscreen operant system. There were no significant differences in an operant conditioning task between genotypes. However, D2L knockout mice were impaired in both visual discrimination and reversal learning tasks. D2L knockout mice were also significantly slower than wild-type mice in collecting the reward in the visual discrimination task. These results indicate that D2L receptors play an important role in visual discrimination and reversal learning.

show abstract

“…Although it was predicted from the inverted U-shaped relationship between DA and cognitive performance that individuals responding positively to amphetamine should have low DA levels at baseline, this is likely to depend on many factors including brain region of interest, DA D1/D2 receptor activation and task features (Floresco, 2013;Klanker et al, 2013). For example, it has been suggested that DA may have opposing roles in the striatum and prefrontal cortex in terms of modulating behavioural flexibility and stability (Cools and D'Esposito, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Human studies demonstrate the importance of considering individual differences in response to pharmacological treatment (Klanker et al, 2013). For example, improvement after amphetamine has been shown to be dependent on baseline performance, such that low performers had the greatest improvement (Mattay et al, 2000;Allman et al, 2010) and this has also been shown for methylphenidate (Finke et al, 2010;del Campo et al, 2013).…”

Section: Significance Statementmentioning

confidence: 99%

“…Irrespective of diagnosis, psychostimulants can improve performance in individuals with low baseline performance and an individual's response has been linked to a range of neurological changes (Mattay et al, 2000;del Campo et al, 2013). Studies have focussed on the role of cortical and striatal brain regions, which are the likely site of neurobiological deficits and medication targets (Mattay et al, 2000;Crofts et al, 2001;Cools and D'Esposito, 2011;Klanker et al, 2013). However, response to DA agonists is paradoxical with positive and negative changes in cognitive performance dependent on dose and task; as well as individual characteristics such as baseline performance, genetics and state when tested (e.g.…”

Section: Significance Statementmentioning

confidence: 99%

See 1 more Smart Citation

Establishing a novel cognitive task in rats of relevance to schizophrenia

Turner¹

View full text Add to dashboard Cite

The most debilitating symptoms for patients with neuropsychiatric disorders, such as schizophrenia, are often cognitive deficits; yet they remain largely untreated by current medications. In preclinical animal models, the techniques used to measure cognitive deficits need to be improved to enhance our ability to screen novel drug targets and gain a better understanding of the neurobiological correlates of cognitive dysfunction. Therefore, the aim of this thesis was to develop and test a new high throughput cognitive task in rodents. I have designed a novel Signal Detection Task (SDT) for this purpose.The first aim in developing the SDT was to compare alternative tasks (such as the 5-choice serial reaction time task) and address limitations including the extensive training time required and the lack of control over body position during stimulus presentation.Experiments were then selected to assess the face, construct and predictive validity of the SDT for measuring attentional deficits relevant to schizophrenia. Specifically, I determined if the effects of genetic, environmental, neurobiological and pharmacological manipulations could be detected in rats using this task. The SDT was conducted in rat operant chambers with a series of task variants to probe different components of performance, such as increasing detection difficulty and distraction. Briefly, the studies conducted compared strains (genetics), housing conditions (environment), the impact of a prefrontal cortical lesion (neurobiology) and the effects of amphetamine (pharmacology) on task performance. My findings indicate a relatively short training period was required for rats to perform the SDT with a high level of accuracy compared to other tasks; task acquisition was shown to be dependent on interactions between genetics and environment; prefrontal cortical lesions did not alter baseline performance but impaired attention during distraction and low dose amphetamine significantly improved accuracy. I demonstrated for the first time that the procognitive effects of amphetamine were dependent on baseline attentional performance. In addition, I found that individual variation in baseline performance was related to dopamine metabolism in the striatum.The research outlined in this thesis presents a novel tool for researchers exploring the cognitive phenotype of animal models relevant to neuropsychiatric disorders and for exploring the neurobiology of attention, including mechanisms of action for procognitive medication.ii Declaration by authorThis thesis is composed of my original work, and contains no material previously published or written by another person except where due reference has been made in the text. I have clearly stated the contribution by others to jointly-authored works that I have included in my thesis.

show abstract

Dopaminergic control of cognitive flexibility in humans and animals

Cited by 188 publications

References 293 publications

A proposed new definition of mental health

A proposed new definition of mental health

Dopamine D2L Receptor Is Required for Visual Discrimination and Reversal Learning

Establishing a novel cognitive task in rats of relevance to schizophrenia

Contact Info

Product

Resources

About