Amphetamine Modestly Improves Conners’ Continuous Performance Test Performance in Healthy Adults

MacQueen, David; Minassian, Arpi; Henry, Brook L.; Geyer, Mark A.; Young, Jared W.; Perry, William

doi:10.1017/s135561771700090x

Cited by 27 publications

(25 citation statements)

References 75 publications

(101 reference statements)

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“…At the present time, a more useful reverse translational exercise is to compare the profiles of AMP, MPH, ATX, and NIC across specific tests conducted between the preclinical and clinical context. AMP has a positive effect on CPT performance both in healthy adults and in individuals diagnosed with ADHD with positive effects on processing speed and attentional domains such as vigilance (Castells et al, 2011a;MacQueen et al, 2018). This shows a translational consistency to the rodent 5-CSRT under conditions such as variable ITI (present study; Bizarro et al, 2004) and extended trials (Grottick and Higgins, 2002).…”

Section: Translational Considerationssupporting

confidence: 72%

Characterization of Amphetamine, Methylphenidate, Nicotine, and Atomoxetine on Measures of Attention, Impulsive Action, and Motivation in the Rat: Implications for Translational Research

Higgins

Silenieks²,

MacMillan³

et al. 2020

Front. Pharmacol.

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Amphetamine (AMP), methylphenidate (MPH), and atomoxetine (ATX) are approved treatments for ADHD, and together with nicotine (NIC), represent pharmacological agents widely studied on cognitive domains including attention and impulsive action in humans. These agents thus represent opportunities for clinical observation to be reinvestigated in the preclinical setting, i.e., reverse translation. The present study investigated each drug in male, Long Evans rats trained to perform either (1) the fivechoice serial reaction time task (5-CSRTT), (2) Go/NoGo task, or (3) a progressive ratio (PR) task, for the purpose of studying each drug on attention, impulsive action and motivation. Specific challenges were adopted in the 5-CSRTT designed to tax attention and impulsivity, i.e., high frequency of stimulus presentation (sITI), variable reduction in stimulus duration (sSD), and extended delay to stimulus presentation (10-s ITI). Initially, performance of a large (> 80) cohort of rats in each task variant was conducted to examine performance stability over repeated challenge sessions, and to identify subgroups of "high" and "low" attentive rats (sITI and sSD schedules), and "high" and "low" impulsives (10-s ITI). Using an adaptive sequential study design, the effects of AMP, MPH, ATX, and NIC were examined and contrasting profiles noted across the tests. Both AMP (0.03-0.3 mg/kg) and MPH (1-6 mg/kg) improved attentional performance in the sITI but not sSD or 10-s ITI condition, NIC (0.05-0.2 mg/kg) improved accuracy across all conditions. ATX (0.1-1 mg/kg) detrimentally affected performance in the sITI and sSD condition, notably in "high" performers. In tests of impulsive action, ATX reduced premature responses notably in the 10-s ITI condition, and also reduced false alarms in Go/NoGo. Both AMP and NIC increased premature responses in all task variants, although AMP reduced false alarms highlighting differences between these two measures of impulsive action. The effect of MPH was mixed and appeared baseline dependent. ATX reduced break point for food reinforcement suggesting a detrimental effect on motivation for primary reward. Taken

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Section: Translational Considerationssupporting

confidence: 72%

Characterization of Amphetamine, Methylphenidate, Nicotine, and Atomoxetine on Measures of Attention, Impulsive Action, and Motivation in the Rat: Implications for Translational Research

Higgins

Silenieks²,

MacMillan³

et al. 2020

Front. Pharmacol.

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“…The present study demonstrates that D-amp improves healthy human performance on the 5CCPT, consistent with traditional CPT variants such as the Conners’ (MacQueen et al, 2017), and consistent with D-amp effects on mouse performance in the 5C-CPT. Overall, performance was improved by D-amp and this effect was largely driven by enhanced hit rate and, reduced omissions.…”

Section: Discussionsupporting

confidence: 83%

“…In healthy subjects, MPD prevented increases in omission errors with time on task (Coons et al, 1981; Strauss et al, 1984) and the progressive decline of signal detection (Strauss et al, 1984). Although D-amp has received considerably less attention than MPD we recently reported similar effects for a 20 mg dose of D-amp on the Conners’ CPT-II, a modern standardized version of the task (MacQueen et al, 2017). In a placebo-controlled, within-subject design, D-amp improved vigilance by preventing decline in signal detection (d’), as well as increased hit (H)RT variability, with time on task.…”

Section: Introductionmentioning

confidence: 89%

“…After consent, participants were screened by a trained clinician for psychiatric illness using the Structured Clinical Interview for DSM-IV (SCID-CT; First et al, 2007). A full description of inclusion/exclusion is provided in MacQueen et al (2017), where we report on D-amp effects across a broader range of tasks in a partially overlapping sample of participants recruited for the D-amp challenge. In brief, participants were excluded for psychiatric illness (including substance use disorders), pregnancy, and health conditions contraindicating D-amp administration.…”

Section: Methodsmentioning

confidence: 99%

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Amphetamine improves mouse and human attention in the 5-choice continuous performance test

et al. 2018

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Non-medical use of prescription stimulants amongst college students is common, with claims of cognitive and academic benefits. The mechanism, magnitude, and pervasiveness of the cognitive enhancing effects of stimulants in healthy adults remain poorly understood however. The present study determined the effects of dextroamphetamine (D-amp) on the 5-choice continuous performance test (5C-CPT) of attention in healthy young adult humans and mice. A mixed gender sample received placebo (n = 29), 10 (n = 17) or 20 mg D-amp (n = 25) in a double-blind fashion before 5C-CPT testing. In addition, male C57BL/6J mice were trained on a touchscreen adaptation of the 5C-CPT and tested after receiving saline or D-amp (0.1, 0.3, 1.0 mg/kg; n = 8/dose). In humans, D-amp significantly improved 5C-CPT performance. Both doses improved signal detection driven by increased hit rate (reduced omissions). Both doses also improved response accuracy and reduced hit reaction time (HRT) variability. In mice, similar effects (improved signal detection, hit rate, and response accuracy) were observed at the moderate dose (0.3 mg/kg). In contrast to human participants however, no effect on HRT variability was detected in mice, with no effect on HRT in either species. Human 5C-CPT performance was consistent with prior studies and consistent with alternative CPT paradigms. The performance of C57BL/6J mice on the touchscreen 5C-CPT mirrored performance of this strain on 5-hole operant chambers. Importantly, comparable facilitation of attention with D-amp was observed in both species. The 5C-CPT provides a cross-species paradigm by which the cognitive enhancing properties of stimulants and the neural underpinnings of attention can be assessed.

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“…4-Fluoroamphetamine improved tracking performance in the divided attention task and decreased reaction time in the spatial memory task. Improvements in attention and motor performance have been reported for many stimulant drugs such as MDMA, amphetamine, and methylphenidate ( Ramaekers et al, 2006 ; Silber et al, 2006 ; Bhattacharya et al, 2015 ; MacQueen et al, 2017 ). We also observed a significant treatment effect on the number of false alarms in the divided attention task.…”

Section: Discussionmentioning

confidence: 99%

Safety Profile and Neurocognitive Function Following Acute 4-Fluoroamphetamine (4-FA) Administration in Humans

et al. 2018

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Availability of novel psychoactive substances (NPS) exponentially increased over the last years. Risk evaluations of NPS are hampered by the lack of pharmacological studies in humans on health parameters. The aim of the present study was to evaluate safety and neurocognitive function of healthy volunteers (N = 12) who received single doses of 100 and 150 mg 4-fluoroamphetamine (4-FA), a phenethylamine that has been associated with severe cardiovascular and cerebrovascular complications. The study was set-up as a placebo controlled, within subject, phase 1 trial as it was the first to administer 4-FA to humans under controlled conditions. Overall, 4-FA produced a strong elevation in blood pressure up until 4–5 h after administration that was followed by a sustained increase in heart rate. After an interim review of safety data from five participants, a decision was taken to cancel administration of 150 mg. We subsequently obtained complete datasets for placebo and 100 mg 4-FA treatments only. Effects of 4-FA on mood and neurocognitive function were most distinct at 1 h post drug and included significant elevations of vigor, friendliness, elation, arousal, positive mood, as well as improvements in attention and motor performance. Negative affect was also reported as time progressed in the acute phase and even more so during the subacute phase. Overall, the influence of 4-FA on vital signs, mood, and neurocognition was similar to that observed with other stimulants. Present findings confirm clinical observations of acute toxicity among 4-FA users and warrant warnings about potential health risks associated with 4-FA use.

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Amphetamine Modestly Improves Conners’ Continuous Performance Test Performance in Healthy Adults

Cited by 27 publications

References 75 publications

Characterization of Amphetamine, Methylphenidate, Nicotine, and Atomoxetine on Measures of Attention, Impulsive Action, and Motivation in the Rat: Implications for Translational Research

Characterization of Amphetamine, Methylphenidate, Nicotine, and Atomoxetine on Measures of Attention, Impulsive Action, and Motivation in the Rat: Implications for Translational Research

Amphetamine improves mouse and human attention in the 5-choice continuous performance test

Safety Profile and Neurocognitive Function Following Acute 4-Fluoroamphetamine (4-FA) Administration in Humans

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