A verification of psychostimulant-induced improvement in sustained attention in rats: Effects of d-amphetamine, nicotine, and pemoline.

Grilly, David M.

doi:10.1037/1064-1297.8.1.14

Cited by 35 publications

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“…Levels of dopamine in the brain have been linked to some measures of sustained attention (Collins, Roberts, Dias, Everitt & Robbins, 1998), and the dopamine agonist amphetamine improves sustained attention in healthy human controls (e.g. Mackworth, 1965;Silber, Croft, Papafotiou & Stough, 2006) and rats (Bizarro, Patel, Murtagh & Stolerman, 2004;Grilly, 2000), as well as ameliorating sustained attention deficits in people with ADHD (Oades, 1987;Sostek, Buchsbaum & Rapoport, 1980;Spencer, Biederman, Wilens, Faraone, Prince, Gerard et al, 2001) and in animal models of the disorder (Chudasama, Nathwani & Robbins, 2005;Sagvolden & Xu, 2008).…”

Section: Introductionmentioning

confidence: 99%

Noradrenergic genotype predicts lapses in sustained attention

et al. 2009

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Publication informationNeuropsychologia, 47 (2): 591-594Publisher Elsevier Item record/more information http://hdl.handle.net/10197/6316 Publisher's statementThis is the author's version of a work that was accepted for publication in Neuropsychologia. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuropsychologia (VOL 47, ISSUE 2, (2009) AbstractSustained attention is modulated by the neurotransmitter noradrenaline. The balance of dopamine and noradrenaline in the cortex is controlled by the DBH gene. The principal variant in this gene is a C/T change at position -1021, and the T allele at this locus is hypothesised to result in a slower rate of dopamine to noradrenaline conversion than the C allele.200 participants who were genotyped for the DBH C-1021T marker performed the Sustained Attention to Response Task (SART). DBH genotype was found to significantly predict performance; participants with more copies of the T allele made more errors of commission, indicative of lapses in sustained attention. A significant negative correlation was also observed for all participants between errors of commission and mean reaction time.The decrease in noradrenaline occasioned by the T allele may impair sustained attention by reducing participants' ability to remain alert throughout the task and by increasing their susceptibility to distractors.

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Section: Introductionmentioning

confidence: 99%

Noradrenergic genotype predicts lapses in sustained attention

et al. 2009

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“…Nonetheless, enhancing attention could improve performance, particularly in the Variable condition because subjects must constantly monitor the environment as they wait for the signal to respond. Amphetamine improves attention (Bizarro et al, 2004;Grilly, 2000) and decreases distractibility (Agmo et al, 1997a, b), which may explain why it improves performance (ie, decreases impulsive action) in the Variable condition, but not in the two Fixed conditions. On the other hand, it may be that amphetamine improves attention in all three conditions, but the effects on impulsive action are masked in the Fixed conditions by drug-induced disruptions in other processes, such as timing or conditioned avoidance.…”

Section: Amphetamine-induced Changes In Impulsive Action May Interactmentioning

confidence: 99%

Opposite Effects of Amphetamine on Impulsive Action with Fixed and Variable Delays to Respond

Hayton

Maracle

Olmstead

2011

Neuropsychopharmacol

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Impulsive action, the failure to withhold an inappropriate response, is treated clinically with dopamine agonists such as amphetamine. Despite the therapeutic efficacy, these drugs have inconsistent effects on impulsive action in rodents, causing improvements or disruptions in different tasks. Thus, we hypothesized that amphetamine is producing an effect by altering distinct cognitive processes in each task. To test this idea, we used the response inhibition (RI) task and trained rats to withhold responding for sucrose until a signal is presented. We then varied the duration that subjects were required to inhibit responding (short ¼ 4 s; long ¼ 60 s; or variable ¼ 1-60 s) and examined whether this influenced the pattern of premature responses. We also tested the effects of amphetamine (0.0, 0.125, 0.25, 0.5, and 1.0 mg/kg) on each task variant. The probability of premature responding varied across the premature interval with a unique pattern of time-dependent errors emerging in each condition. Amphetamine also had distinct effects on each version: the drug promoted premature responding when subjects expected a consistent delay, regardless of its duration, but reduced premature responding when the delay was unpredictable. We propose that the ability to inhibit a motor response is controlled by a different combination of cognitive processes in the three task conditions. These include timing, conditioned avoidance, and attention, which then interact with amphetamine to increase or decrease impulsive action. The effect of amphetamine on impulsive action, therefore, is not universal, but depends on the subject's experience and expectation of the task demands.

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“…Demonstrating improved performance after low dose amphetamine supports the predictive validity of this task and demonstrates that systemic amphetamine can enhance attention in adult rats (Young et al, 2009a). There are relatively few studies demonstrating enhancement of attention with systemic low dose amphetamine in rats (Grilly, 2000;Grottick and Higgins, 2002;Chudasama et al, 2005;Andrzejewski et al, 2014). Therefore, given the widespread use of psychostimulant agents in attentional disorders (Wolraich et al, 2005) and the clinical importance of predictive validity in animal models (Hagan and Jones, 2005;Pratt et al, 2012), these results are promising and should be further explored.…”

Section: Discussionmentioning

confidence: 94%

“…Therefore, investigating the response to psychostimulants as a function of individual baseline performance should be incorporated into rodent studies, as a similar relationship should be expected (Levin et al, 2011). There are limited studies reporting attentional improvement in rats after systemic amphetamine (Grilly et al, 1998;Grilly, 2000;Grottick and Higgins, 2002;Andrzejewski et al, 2014). There are even fewer studies reporting baseline-dependent effects of amphetamine on cognition.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, a number of studies have demonstrated improved cognitive performance in schizophrenia patients when amphetamine was acutely given in combination with antipsychotic medication (Barch and Carter, 2005;Pietrzak et al, 2010). Despite the successful use of amphetamine in ADHD patients, few preclinical studies have demonstrated attentional improvements in rodents (Grilly, 2000;Bizarro et al, 2004;Andrzejewski et al, 2014). A task that can reliably detect procognitive effects on attention would allow researchers to explore the paradoxical effects of psychostimulant response and also screen novel compounds for improving attention.…”

Section: Introductionmentioning

confidence: 99%

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Establishing a novel cognitive task in rats of relevance to schizophrenia

Turner¹

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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.

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A verification of psychostimulant-induced improvement in sustained attention in rats: Effects of d-amphetamine, nicotine, and pemoline.

Cited by 35 publications

References 41 publications

Noradrenergic genotype predicts lapses in sustained attention

Noradrenergic genotype predicts lapses in sustained attention

Opposite Effects of Amphetamine on Impulsive Action with Fixed and Variable Delays to Respond

Establishing a novel cognitive task in rats of relevance to schizophrenia

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