Measuring impulsivity in mice: the five-choice serial reaction time task

Sanchez‐Roige, Sandra; Peña-Oliver, Yolanda; Stephens, David

doi:10.1007/s00213-011-2560-5

Cited by 61 publications

(51 citation statements)

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“…These two test conditions challenge the performance of The influence of test experience and NK1 receptor antagonists on the performance of NK1R-/-and wild type mice in the 5-Choice Serial Reaction-Time Task mice in the 5-CSRTT in different ways (Humby et al, 2005;Patel et al, 2006;Sanchez-Roige et al, 2012). In particular, in the VITI, it is not possible to predict when the light cue will appear after trial initiation, and so this test avoids the potential confound of animals using interval-timing to prompt their responses, which is thought to occur with the LITI (Praamstra et al, 2006;Sanchez-Roige et al, 2012). Because these two test conditions seem to reveal different performance deficits (Yan et al, 2011), we thought it advisable to test mice under both conditions.…”

Section: Introductionmentioning

confidence: 99%

The influence of test experience and NK1 receptor antagonists on the performance of NK1R-/- and wild type mice in the 5-Choice Serial Reaction-Time Task

et al. 2013

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Genetically-altered mice, lacking functional NK1 receptors (NK1R-/-), express abnormal behaviours that are prominent in Attention Deficit Hyperactivity Disorder: namely, inattentiveness and impulsivity (indicated by their greater % omissions and premature responses in the 5-Choice Serial ReactionTime Task (5-CSRTT) and locomotor hyperactivity. We investigated how behaviour in the 5-CSRTT is affected by repeated testing and whether the abnormalities expressed by NK1R-/-mice are mimicked by treating wild type mice with a NK1R antagonist (L 733060 or RP 67580; 5 or 10 mg/kg). Repeated testing with a variable (VITI) or fixed, prolonged (LITI) intertrial interval reduced % omissions. Premature responses also declined, but only in NK1R-/-mice, in the VITI test. By contrast, perseveration increased in both genotypes. RP 67580 (10 mg/kg) increased the % omissions in both genotypes in the VITI, an action which cannot be attributed to NK1R antagonism. Neither drug affected perseveration. However, for premature responses, the response profile suggested that the low and high doses of RP 67580 (VITI) and L 733060 (LITI) had opposing effects on this behaviour. We infer that the effect of NK1R antagonists in the 5-CSRTT is confounded by animals' test experience and non-specific drug effects at sites other than NK1R, possibly L-type Ca 2+ v channels.

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Section: Introductionmentioning

confidence: 99%

The influence of test experience and NK1 receptor antagonists on the performance of NK1R-/- and wild type mice in the 5-Choice Serial Reaction-Time Task

et al. 2013

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“…Performance decrements can occur for a number of reasons so other variables were carefully considered to determine the likely reason for reduced accuracy. We found that the number of omissions increased when accuracy decreased during the variable signal durations on the 5CSRTT, which was also found by Fletcher et al (2007) and has been reported in mice (Sanchez-Roige et al, 2012). Both the response latency and reward latency were unchanged in the 5CSRTT across the session indicating variable stimulus durations do not alter response speed, which is also in agreement with the literature (Fletcher et al, 2007).…”

Section: Discussionsupporting

confidence: 82%

“…Although the SAT results in far fewer omission responses than the 5CSRTT and 5C-CPT, the application of this task to mice has been challenging (Martin et al, 2006;St Peters et al, 2011a). However, mice have been used in both the 5CSRTT and 5C-CPT (Young et al, 2009b;Harms et al, 2012;Sanchez-Roige et al, 2012). With a focus on translational testing, it is important to acknowledge that each of these protocols have similarities and differences when compared to human CPT testing.…”

Section: Rodent Tasks 151 Current Tasksmentioning

confidence: 99%

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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“…Testing of performance followed the protocol previously described (Pena-Oliver et al, 2012; see Supplementary Methods). In brief, following training under fITI conditions, mice were tested under vITI (2, 5, 10, 15 s) conditions to increase premature responding (Robbins, 2002;Sanchez-Roige et al, 2012).…”

Section: Mouse Studymentioning

confidence: 99%

Exaggerated Waiting Impulsivity Associated with Human Binge Drinking, and High Alcohol Consumption in Mice

Sanchez‐Roige

Baro

Trick

et al. 2014

Neuropsychopharmacol

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There are well-established links between impulsivity and alcohol use in humans and animal models; however, whether exaggerated impulsivity is a premorbid risk factor or a consequence of alcohol intake remains unclear. In a first approach, human young (18-25 years) social binge and non-binge drinkers were tested for motor impulsivity and attentional abilities in a human version of the Five-Choice Serial Reaction Time Task (Sx-5CSRTT), modeled on the rodent 5CSRTT. Participants completed four variants of the Sx-5CSRT, in addition to being screened for impulsive traits (BIS-11 questionnaire) and impulsive behavior (by means of the Delay Discounting Questionnaire, Two-Choice Impulsivity Paradigm (TCIP), Stop Signal Reaction Time, and Time Estimation Task). Using a second approach, we compared one of these impulsivity measures, 5CSRTT performance, in two inbred strains of mice known to differ in alcohol intake. Compared with non-bingers (NBD; n ¼ 22), binge drinkers (BD, n ¼ 22) showed robust impairments in attention and premature responding when evaluated under increased attentional load, in addition to presenting deficits in decision making using the TCIP. The best predictors for high binge drinking score were premature responding in the Sx-5CSRTT, trait impulsivity in the BIS-11, and decision making in the TCIP. Alcohol-naïve C57BL/6J (B6) mice (alcohol preferring) were more impulsive in the 5CSRTT than DBA2/J (D2) mice (alcohol averse); the degree of impulsivity correlated with subsequent alcohol consumption. Homologous measures in animal and human studies indicate increased premature responding in young social BD and in the ethanol-preferring B6 strain of mice.

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Measuring impulsivity in mice: the five-choice serial reaction time task

Abstract: The 5CSRTT has proven to be a useful tool to investigate impulsivity in mice.

Cited by 61 publications

References 68 publications

The influence of test experience and NK1 receptor antagonists on the performance of NK1R-/- and wild type mice in the 5-Choice Serial Reaction-Time Task

The influence of test experience and NK1 receptor antagonists on the performance of NK1R-/- and wild type mice in the 5-Choice Serial Reaction-Time Task

Establishing a novel cognitive task in rats of relevance to schizophrenia

Exaggerated Waiting Impulsivity Associated with Human Binge Drinking, and High Alcohol Consumption in Mice

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