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Paul J Fletcher - One of the best experts on this subject based on the ideXlab platform.
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kappa opioid receptors mediate yohimbine induced increases in impulsivity in the 5 choice Serial Reaction Time task
Behavioural Brain Research, 2019Co-Authors: Douglas Funk, Paul J Fletcher, Sahar Tamadon, Kathy CoenAbstract:Abstract Dynorphin (DYN), and its receptor, the kappa opioid receptor (KOR) are involved in drug seeking and relapse but the mechanisms are poorly understood. One hypothesis is that DYN/KOR activation promotes drug seeking through increased impulsivity, because many stimuli that induce DYN release increase impulsivity. Here, we systematically compare the effects of drugs that activate DYN/KOR on performance on the 5-choice Serial Reaction Time task (5-CSRTT), a test of sustained attention and impulsivity. In Experiment 1, we determined the effects of U50,488 (0, 2.5, 5 mg/kg), yohimbine (0, 1.25, 2.5 mg/kg), and nicotine (0, 0.15, 0.3 mg/kg) on 5-CSRTT performance. In Experiment 2, we determined the effects of alcohol (0, 0.5, 1.0, 1.5 g/kg) on 5-CSRTT performance before and after voluntary, intermittent alcohol exposure. In Experiment 3, we determined the potential role of KOR in the pro-impulsive effects of yohimbine (1.25 mg/kg) and nicotine (0.3 mg/kg) by the prior administration of the KOR antagonist nor-BNI (10 mg/kg). Premature responding, the primary measure of impulsivity, was reduced by U50,488 and alcohol, but these drugs had a general suppressive effect. Yohimbine and nicotine increased premature responding. Yohimbine-, but not nicotine-induced increases in premature responding were blocked by nor-BNI, suggesting that impulsivity induced by yohimbine is KOR dependent. This may suggests a potential role for KOR-mediated increases in impulsivity in yohimbine-induced reinstatement.
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kappa opioid receptors mediate yohimbine induced increases in impulsivity in the 5 choice Serial Reaction Time task
Behavioural Brain Research, 2019Co-Authors: Douglas Funk, Paul J Fletcher, Sahar Tamadon, Kathy Coen, A D LeAbstract:Abstract Dynorphin (DYN), and its receptor, the kappa opioid receptor (KOR) are involved in drug seeking and relapse but the mechanisms are poorly understood. One hypothesis is that DYN/KOR activation promotes drug seeking through increased impulsivity, because many stimuli that induce DYN release increase impulsivity. Here, we systematically compare the effects of drugs that activate DYN/KOR on performance on the 5-choice Serial Reaction Time task (5-CSRTT), a test of sustained attention and impulsivity. In Experiment 1, we determined the effects of U50,488 (0, 2.5, 5 mg/kg), yohimbine (0, 1.25, 2.5 mg/kg), and nicotine (0, 0.15, 0.3 mg/kg) on 5-CSRTT performance. In Experiment 2, we determined the effects of alcohol (0, 0.5, 1.0, 1.5 g/kg) on 5-CSRTT performance before and after voluntary, intermittent alcohol exposure. In Experiment 3, we determined the potential role of KOR in the pro-impulsive effects of yohimbine (1.25 mg/kg) and nicotine (0.3 mg/kg) by the prior administration of the KOR antagonist nor-BNI (10 mg/kg). Premature responding, the primary measure of impulsivity, was reduced by U50,488 and alcohol, but these drugs had a general suppressive effect. Yohimbine and nicotine increased premature responding. Yohimbine-, but not nicotine-induced increases in premature responding were blocked by nor-BNI, suggesting that impulsivity induced by yohimbine is KOR dependent. This may suggests a potential role for KOR-mediated increases in impulsivity in yohimbine-induced reinstatement.
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impulsive action in the 5 choice Serial Reaction Time test in 5 ht2c receptor null mutant mice
Psychopharmacology, 2013Co-Authors: Paul J Fletcher, Ashlie D Soko, Guy A HigginsAbstract:Rationale Depletion of brain serotonin (5-HT) results in impulsive behaviour as measured by increased premature responding in the five-choice Serial Reaction Time (5-CSRT) test. Acute selective blockade of 5-HT2C receptors also increases this form of impulsive action, whereas 5-HT2C receptor stimulation reduces premature responding.
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impulsive action in the 5 choice Serial Reaction Time test in 5 ht 2c receptor null mutant mice
Psychopharmacology, 2013Co-Authors: Paul J Fletcher, Ashlie D Soko, Guy A HigginsAbstract:Depletion of brain serotonin (5-HT) results in impulsive behaviour as measured by increased premature responding in the five-choice Serial Reaction Time (5-CSRT) test. Acute selective blockade of 5-HT2C receptors also increases this form of impulsive action, whereas 5-HT2C receptor stimulation reduces premature responding. These experiments determined the impact of genetic disruption of 5-HT2C receptor function on impulsive responding in the 5-CSRT test. Food-restricted 5-HT2C receptor null mutant and wild-type (WT) mice were trained on the 5-CSRT test in which subjects detect and correctly respond to brief light stimuli for food reinforcement. Impulsivity is measured as premature responses that occur prior to stimulus presentation. Both lines of mice quickly learned this task, but there were no genotype differences in premature responding or any other aspect of performance. A series of drug challenges were then given. The 5-HT2C receptor agonist Ro60-0175 (0.6 mg/kg) reduced premature responding in WT mice but not mutant mice. The 5-HT2C receptor antagonist SB242084 increased premature responding in WT mice only. Cocaine increased premature responding at 7.5 mg/kg but not at a higher dose that disrupted overall responding; these effects were observed in both lines of mice. Amphetamine (0.25 and 0.5 mg/kg) did not affect premature responding, but disrupted other aspects of performance in both genotypes. Genetic deletion of 5-HT2C receptor function does not induce an impulsive state or exacerbate that state induced by psychomotor stimulants but does prevent the acute effects of 5-HT2C receptor stimulation or blockade on impulsive action.
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a sensitizing regimen of amphetamine impairs visual attention in the 5 choice Serial Reaction Time test reversal by a d1 receptor agonist injected into the medial prefrontal cortex
Neuropsychopharmacology, 2007Co-Authors: Paul J Fletcher, Catherine C Tenn, Judy Sinyard, Zoe Rizos, Shitij KapurAbstract:A Sensitizing Regimen of Amphetamine Impairs Visual Attention in the 5-Choice Serial Reaction Time Test: Reversal by a D1 Receptor Agonist Injected into the Medial Prefrontal Cortex
Guy A Higgins - One of the best experts on this subject based on the ideXlab platform.
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rodent test of attention and impulsivity the 5 choice Serial Reaction Time task
Current protocols in pharmacology, 2017Co-Authors: Guy A Higgins, Leo B SilenieksAbstract:: The 5-choice Serial Reaction Time task (5-CSRTT) is employed extensively to measure attention in rodents. The assay involves animals trained to respond to a brief, unpredictable visual stimulus presented in one of five locations. The effects of experimental manipulations on response speed and choice accuracy are measured, and each related to attentional performance. The 5-CSRTT is also used to measure motor impulsivity. Adapted from a human task, the 5-CSRTT can be employed with rodents or primates, highlighting its translational value. Another strength of this procedure is its adaptability to task modification. An example is the 5-choice continuous performance task, which has both target and non-target trial types. Overall, the 5-CSRTT has proven to be valuable for drug discovery efforts aimed at identifying new agents for the treatment of central nervous system disorders and for further understanding the neurobiological processes of attention and impulsivity. Its flexibility offers considerable scope to the experimenter, and in this respect the task continues to evolve. © 2017 by John Wiley & Sons, Inc.
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impulsive action in the 5 choice Serial Reaction Time test in 5 ht2c receptor null mutant mice
Psychopharmacology, 2013Co-Authors: Paul J Fletcher, Ashlie D Soko, Guy A HigginsAbstract:Rationale Depletion of brain serotonin (5-HT) results in impulsive behaviour as measured by increased premature responding in the five-choice Serial Reaction Time (5-CSRT) test. Acute selective blockade of 5-HT2C receptors also increases this form of impulsive action, whereas 5-HT2C receptor stimulation reduces premature responding.
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impulsive action in the 5 choice Serial Reaction Time test in 5 ht 2c receptor null mutant mice
Psychopharmacology, 2013Co-Authors: Paul J Fletcher, Ashlie D Soko, Guy A HigginsAbstract:Depletion of brain serotonin (5-HT) results in impulsive behaviour as measured by increased premature responding in the five-choice Serial Reaction Time (5-CSRT) test. Acute selective blockade of 5-HT2C receptors also increases this form of impulsive action, whereas 5-HT2C receptor stimulation reduces premature responding. These experiments determined the impact of genetic disruption of 5-HT2C receptor function on impulsive responding in the 5-CSRT test. Food-restricted 5-HT2C receptor null mutant and wild-type (WT) mice were trained on the 5-CSRT test in which subjects detect and correctly respond to brief light stimuli for food reinforcement. Impulsivity is measured as premature responses that occur prior to stimulus presentation. Both lines of mice quickly learned this task, but there were no genotype differences in premature responding or any other aspect of performance. A series of drug challenges were then given. The 5-HT2C receptor agonist Ro60-0175 (0.6 mg/kg) reduced premature responding in WT mice but not mutant mice. The 5-HT2C receptor antagonist SB242084 increased premature responding in WT mice only. Cocaine increased premature responding at 7.5 mg/kg but not at a higher dose that disrupted overall responding; these effects were observed in both lines of mice. Amphetamine (0.25 and 0.5 mg/kg) did not affect premature responding, but disrupted other aspects of performance in both genotypes. Genetic deletion of 5-HT2C receptor function does not induce an impulsive state or exacerbate that state induced by psychomotor stimulants but does prevent the acute effects of 5-HT2C receptor stimulation or blockade on impulsive action.
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rodent model of attention the 5 choice Serial Reaction Time task
Current protocols in pharmacology, 2008Co-Authors: Guy A Higgins, Nathalie BreysseAbstract:The 5-choice Serial Reaction Time task (5-CSRTT) is the most widely used test to measure attentional performance in rodents. The basic test design involves training animals to respond to a brief visual stimulus presented unpredictably in one of five locations. Once trained to stable performance levels, the effects of experimental manipulations on response speed and choice accuracy are measured and each are related to attentional performance. Increasingly, the test is also used to examine aspects of response control. Having been adapted from a human task, the test has also been successfully extended to the mouse and primate, thus highlighting its translational value. Increasingly this test is being applied in drug discovery efforts, primarily to identify novel drug treatments for conditions associated with attention deficits. Curr. Protoc. Pharmacol. 41:5.49.1-5.49.20. © 2008 by John Wiley & Sons, Inc. Keywords: attention; cognition; methodology; rat; mouse; drug discovery; nicotine
Trevor W Robbins - One of the best experts on this subject based on the ideXlab platform.
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serotonin depletion induces waiting impulsivity on the human four choice Serial Reaction Time task cross species translational significance
Neuropsychopharmacology, 2014Co-Authors: Yulia Worbe, George Savulich, Valerie Voon, Emilio Fernandezegea, Trevor W RobbinsAbstract:Serotonin Depletion Induces ‘Waiting Impulsivity’ on the Human Four-Choice Serial Reaction Time Task: Cross-Species Translational Significance
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opposing roles for 5 ht2a and 5 ht2c receptors in the nucleus accumbens on inhibitory response control in the 5 choice Serial Reaction Time task
Neuropsychopharmacology, 2008Co-Authors: Emma S J Robinson, Jeffrey W Dalley, Marieastrid Pezze, David E H Theobald, Jeffrey C Glennon, Emily R Murphy, Trevor W RobbinsAbstract:Opposing Roles for 5-HT 2A and 5-HT 2C Receptors in the Nucleus Accumbens on Inhibitory Response Control in the 5-Choice Serial Reaction Time Task
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The application of the 5-choice Serial Reaction Time task for the assessment of visual attentional processes and impulse control in rats
Nature Protocols, 2008Co-Authors: Andrea Bari, Jeffrey W Dalley, Trevor W RobbinsAbstract:One popular way of measuring visual attentional processes in the rat is using 5-choice Serial Reaction Time task (5-CSRTT). This paradigm requires subjects to detect brief flashes of light presented in a pseudorandom order in one of five spatial locations over a large number of trials. For this task, the animals are trained for ∼30–40 daily sessions during which they gradually learn to respond in the appropriate aperture within a certain amount of Time. If they fail to respond, respond in the wrong hole or at an inappropriate Time, a short period of darkness (Time-out) is presented as punishment and no reward is delivered. The 5-CSRTT provides the possibility to test the effects of various neural, pharmacological and behavioral manipulations on discrete and somewhat independent measures of behavioral control, including accuracy of discrimination, impulsivity, perseverative responses and response latencies.
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the application of the 5 choice Serial Reaction Time task for the assessment of visual attentional processes and impulse control in rats
Nature Protocols, 2008Co-Authors: Andrea Bari, Jeffrey W Dalley, Trevor W RobbinsAbstract:The application of the 5-choice Serial Reaction Time task for the assessment of visual attentional processes and impulse control in rats
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differential roles of dopamine d1 and d2 receptors in the nucleus accumbens in attentional performance on the five choice Serial Reaction Time task
Neuropsychopharmacology, 2007Co-Authors: Marieastrid Pezze, Jeffrey W Dalley, Trevor W RobbinsAbstract:Differential Roles of Dopamine D1 and D2 Receptors in the Nucleus Accumbens in Attentional Performance on the Five-Choice Serial Reaction Time Task
Eli Vakil - One of the best experts on this subject based on the ideXlab platform.
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oculomotor anticipation reveals a multitude of learning processes underlying the Serial Reaction Time task
Scientific Reports, 2021Co-Authors: Ayala Bloch, Simone Schwizer Ashkenazi, Amir Tal, Haggar Cohendallal, Or Aviv, Moshe Bar, Eli VakilAbstract:Sequence learning is the cognitive faculty enabling everyday skill acquisition. In the lab, it is typically measured in speed of response to sequential stimuli, whereby faster responses are taken to indicate improved anticipation. However, response speed is an indirect measure of anticipation, that can provide only limited information on underlying processes. As a result, little is known about what is learned during sequence learning, and how that unfolds over Time. In this work, eye movements that occurred before targets appeared on screen in an ocular Serial Reaction Time (O-SRT) task provided an online indication of where participants anticipated upcoming targets. When analyzed in the context of the stimuli preceding them, oculomotor anticipations revealed several simultaneous learning processes. These processes influenced each other, as learning the task grammar facilitated acquisition of the target sequence. However, they were dissociable, as the grammar was similarly learned whether a repeating sequence inhabited the task or not. Individual differences were found in how the different learning processes progressed, allowing for similar performance to be produced for different latent reasons. This study provides new insights into the processes subserving sequence learning, and a new method for high-resolution study of it.
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examining implicit procedural learning in tetraplegia using an oculomotor Serial Reaction Time task
PLOS ONE, 2020Co-Authors: Ayala Bloch, Eli Vakil, Michal Shaham, Simone Schwizer Ashkenazi, Gabi ZeiligAbstract:Background and objective Clinical observations indicate that implicit procedural learning, a central component of physical and psychosocial rehabilitation, is impeded following spinal cord injury. In accordance, previous research has revealed a specific deficit in implicit sequence learning among individuals with paraplegia using a standard, manual version of the Serial Reaction Time task. To extend these findings and shed light on the underlying sources of potential spinal cord injury-related deficits in sequence learning, we used an ocular activated Serial Reaction Time task to compare sequence learning performance between individuals with tetraplegia and healthy controls. Participants and measures Twelve participants with spinal cord injury in C5-T1 were compared to 12 matched control participants on measures derived from an ocular activated Serial Reaction Time task. Depression and additional cognitive measures were assessed to explore the source and specificity of potential sequence learning deficits. Results Like controls, and in contrast with previous findings in paraplegia, the spinal cord injury group showed intact implicit sequence learning, evidenced by declining Reaction Times and improved anticipation over the first six blocks of the Serial Reaction Time task, and an advantage for the initial learning sequence over a novel interference sequence. Conclusions The ocular activated Serial Reaction Time task elicited a performance pattern similar to standard motor versions, such that participants with tetraplegia demonstrated unimpaired sequence learning. This suggests that previously reported implicit sequence learning deficits in spinal cord injury directly involved motor functioning rather than cognitive aspects of the task, and that the ocular activated sequence learning task could be a valid alternative for assessing implicit sequence learning in populations that cannot perform spinal-cord dependent motor tasks. Implications for post-spinal cord injury rehabilitation and adjustment are discussed.
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anticipation measures of sequence learning manual versus oculomotor versions of the Serial Reaction Time task
Quarterly Journal of Experimental Psychology, 2017Co-Authors: Eli Vakil, Ayala Bloch, Haggar CohenAbstract:ABSTRACTThe Serial Reaction Time (SRT) task has generated a very large amount of research. Nevertheless the debate continues as to the exact cognitive processes underlying implicit sequence learning. Thus, the first goal of this study is to elucidate the underlying cognitive processes enabling sequence acquisition. We therefore compared Reaction Time (RT) in sequence learning in a standard manual activated (MA) to that in an ocular activated (OA) version of the task, within a single experimental setting. The second goal is to use eye movement measures to compare anticipation, as an additional indication of sequence learning, between the two versions of the SRT. Performance of the group given the MA version of the task (n = 29) was compared with that of the group given the OA version (n = 30). The results showed that although overall, RT was faster for the OA group, the rate of sequence learning was similar to that of the MA group performing the standard version of the SRT. Because the stimulus-response as...
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motor and non motor sequence learning in patients with basal ganglia lesions the case of Serial Reaction Time srt
Neuropsychologia, 2000Co-Authors: Eli Vakil, Shimon Kahan, Moshe Huberman, Alicia OsimaniAbstract:In order to address the question of whether the basal ganglia are involved exclusively in regulation of motor sequence learning, or if they are involved in non-motor sequence learning as well, two versions of the Serial Reaction Time (SRT) task were administered: First is the standard version of the SRT task in which the sequence is executed motorically, and the second is a non-motor version of the task which requires response only to a particular position of the sequence. Sixteen patients with damage restricted to the region of the basal ganglia and 16 matched control subjects participated in this study. In addition to the motor and non-motor SRT tasks, two declarative memory tests (Visual Paired Associates and Rey Auditory-Verbal Learning Test) were administered to the participants. Results indicate that the two groups did not differ either on learning rate of the two declarative tasks, or on the declarative component of the SRT tasks (i.e., 'generate'). However, the control group was significantly superior to the basal ganglia (BG) group in learning a specific sequence in the motor and non-motor SRT tasks. Results suggest that the basal ganglia are involved in the regulation of non- motor as well as motor sequence learning.
Jesper T Andreasen - One of the best experts on this subject based on the ideXlab platform.
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differential effects of adhd medications on impulsive action in the mouse 5 choice Serial Reaction Time task
European Journal of Pharmacology, 2019Co-Authors: Ciaran M Fitzpatrick, Jesper T AndreasenAbstract:Abstract Aberrant impulsivity is found in a number of psychiatric disorders including attention deficit hyperactivity disorder (ADHD). The 5-choice Serial Reaction Time task (5-CSRTT) is a paradigm commonly used to assess impulsive control. We recently developed a protocol to habituate mice to a variable intertrial interval (vITI) schedule before assessing pharmacological effects on “waiting” impulsivity. This study aimed to develop on that initial investigation by testing the effects of three conventional ADHD medications. Consistent premature response rates were achieved in male C57BL/6 J mice in the first week out of 15 vITI (5-, 10- or 15-s) days (four training days followed by one drug treatment day per week for three weeks) before each drug study commenced. The effects of atomoxetine (1, 3 mg/kg), methylphenidate (1, 2 mg/kg) and guanfacine (0.03, 0.1 mg/kg) were investigated using a Latin-square design. High- and low-impulsive subgroups were determined based on initial training day data before the drug studies initiated. Both 1 and 3 mg/kg atomoxetine reduced premature responding at the 10- (P
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effects of amphetamine and methylphenidate on attentional performance and impulsivity in the mouse 5 choice Serial Reaction Time task
Journal of Psychopharmacology, 2017Co-Authors: Maitane Caballeropuntiverio, Ciaran M Fitzpatrick, David P D Woldbye, Jesper T AndreasenAbstract:Background:Few studies have investigated the effects of conventional attention deficit-hyperactivity disorder (ADHD) medication in the mouse 5-choice Serial Reaction Time task (5-CSRTT), and rat st...
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theory of visual attention tva applied to mice in the 5 choice Serial Reaction Time task
Psychopharmacology, 2017Co-Authors: Ciaran M Fitzpatrick, Maitane Caballeropuntiverio, Ulrik Gether, Thomas Habekost, Claus Bundesen, Signe Vangkilde, David P D Woldbye, Jesper T Andreasen, Anders PetersenAbstract:Rationale The 5-choice Serial Reaction Time task (5-CSRTT) is widely used to measure rodent attentional functions. In humans, many attention studies in healthy and clinical populations have used testing based on Bundesen’s Theory of Visual Attention (TVA) to estimate visual processing speeds and other parameters of attentional capacity.
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theory of visual attention tva applied to mice in the 5 choice Serial Reaction Time task
Psychopharmacology, 2017Co-Authors: Ciaran M Fitzpatrick, Maitane Caballeropuntiverio, Ulrik Gether, Thomas Habekost, Claus Bundesen, Signe Vangkilde, David P D Woldbye, Jesper T Andreasen, Anders PetersenAbstract:The 5-choice Serial Reaction Time task (5-CSRTT) is widely used to measure rodent attentional functions. In humans, many attention studies in healthy and clinical populations have used testing based on Bundesen’s Theory of Visual Attention (TVA) to estimate visual processing speeds and other parameters of attentional capacity. We aimed to bridge these research fields by modifying the 5-CSRTT’s design and by mathematically modelling data to derive attentional parameters analogous to human TVA-based measures. C57BL/6 mice were tested in two 1-h sessions on consecutive days with a version of the 5-CSRTT where stimulus duration (SD) probe length was varied based on information from previous TVA studies. Thereafter, a scopolamine hydrobromide (HBr; 0.125 or 0.25 mg/kg) pharmacological challenge was undertaken, using a Latin square design. Mean score values were modelled using a new three-parameter version of TVA to obtain estimates of visual processing speeds, visual thresholds and motor response baselines in each mouse. The parameter estimates for each animal were reliable across sessions, showing that the data were stable enough to support analysis on an individual level. Scopolamine HBr dose-dependently reduced 5-CSRTT attentional performance while also increasing reward collection latency at the highest dose. Upon TVA modelling, scopolamine HBr significantly reduced visual processing speed at both doses, while having less pronounced effects on visual thresholds and motor response baselines. This study shows for the first Time how 5-CSRTT performance in mice can be mathematically modelled to yield estimates of attentional capacity that are directly comparable to estimates from human studies.
