Differences in trait impulsivity do not bias the response to pharmacological drug challenge in the rat five-choice serial reaction time task

Barlow, Rebecca; Dalley, Jeffrey W.; Pekcec, Anton

doi:10.1007/s00213-018-4836-5

Cited by 16 publications

(13 citation statements)

References 56 publications

(72 reference statements)

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“…Pretreatments with cocaine or MDPV tended to increase measures of impulsivity in HI rats but not consistently and not at significant levels. This finding is similar to what has been reported before in experiments with cocaine 38,39 . Hyatt et al (2019), one of the first papers to describe the effects of MDPV on impulsivity, found that acute administration of MDPV, but not cocaine, led to increases in choice impulsivity in a delay‐discounting task 40 .…”

Section: Discussionsupporting

confidence: 87%

Interactions between impulsivity and MDPV self‐administration in rats

et al. 2022

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Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone (MDPV), are recreational drugs of abuse often identified in 'bath salts' preparations. Humans report compulsive patterns of bath salts use, and previous work suggests that a subset of rats develop unusually high levels of MDPV self-administration. This study aims to test the hypothesis that high levels of impulsivity (e.g., inability to withhold responding for a sucrose reward) will predispose rats to high levels of MDPV self-administration relative to rats with lower levels of impulsivity. The 1-choice serial reaction time task (1-CSRTT) was used to assess impulsivity (i.e., premature responding) in 10 female and 10 male Sprague Dawley rats. Rats were then allowed to self-administer 0.032 mg/kg/inf MDPV or 0.32 mg/kg/inf cocaine, after which full dose-response curves for MDPV (0.001-0.1 mg/kg/inf ) or cocaine (0.01-1 mg/kg/inf) were generated under a FR5 schedule of reinforcement. After a history of self-administering MDPV or cocaine, impulsivity was reassessed under the 1-CSRTT, prior to evaluating the acute effects of MDPV (0.032-0.32 mg/kg) or cocaine (0.1-1 mg/kg) on impulsivity. Level of impulsivity was not correlated with subsequent levels of either MDPV or cocaine selfadministration, and level of drug self-administration was also not correlated with subsequent levels of impulsivity, although acute administration of MDPV and cocaine did increase premature responding. In failing to find direct relationships between either impulsivity and subsequent drug-taking behaviour, or drug-taking behaviour and subsequent assessments of impulsivity, these findings highlight the complexity inherent in the associations between impulsive behaviour and drug-taking behaviour in both animal models and humans.

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Section: Discussionsupporting

confidence: 87%

Interactions between impulsivity and MDPV self‐administration in rats

et al. 2022

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“…≤10%). However, lengthening the ITI from 5 to 10 s produced a dramatic increase in premature responses, a consistent finding that has been widely reported (Robbins, 2002;Blondeau and Dellu-Hagedorn, 2007;Higgins and Silenieks, 2017;Barlow et al, 2018). Accuracy was also reduced at the longer ITI compared to 5-s ITI, although whether this is a consequence of the lower SD (5-s ITI SD=0.75 s; 10-s ITI SD=0.3 s), or longer ITI, or both, is unclear from the present experiments.…”

Section: Characterization Of Performance Across the Five-choice Challsupporting

confidence: 88%

“…Subgrouping rats under the 10-s ITI schedule based on the level of premature responses into "Low" and "High" impulsives (LI vs. HI) highlighted the wide range of responders on this parameter (Dalley et al, 2007;Barlow et al, 2018). Importantly there was a reasonable consistency of performance on this measure over repeated tests.…”

Section: Characterization Of Performance Across the Five-choice Challmentioning

confidence: 90%

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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“…The principal challenge is to response control, lengthening the ITI from 5 s to 10 s produces a significant increase in both PREM and PSV responses, a consistent and widely reported finding (Robbins, 2002;Jupp et al, 2013;Barlow et al, 2018;Higgins et al, 2020a,b). Subgrouping rats, based on the level of PREM responses under the 10 s ITI schedule, into "Low" and "High" impulsives (LI vs. HI) highlights a wide range of responders typically seen under this schedule (Jupp et al, 2013;Fink et al, 2015;Barlow et al, 2018;Higgins et al, 2020a). Importantly there is a reasonable consistency of performance on this measure over repeated tests as demonstrated by the HI rats having higher PREM scores under the 5 s ITI, albeit at markedly lower levels.…”

Section: Discussionsupporting

confidence: 59%

Low Doses of Psilocybin and Ketamine Enhance Motivation and Attention in Poor Performing Rats: Evidence for an Antidepressant Property

Higgins¹,

Carroll²,

Brown³

et al. 2021

Front. Pharmacol.

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Long term benefits following short-term administration of high psychedelic doses of serotonergic and dissociative hallucinogens, typified by psilocybin and ketamine respectively, support their potential as treatments for psychiatric conditions such as major depressive disorder. The high psychedelic doses induce perceptual experiences which are associated with therapeutic benefit. There have also been anecdotal reports of these drugs being used at what are colloquially referred to as “micro” doses to improve mood and cognitive function, although currently there are recognized limitations to their clinical and preclinical investigation. In the present studies we have defined a low dose and plasma exposure range in rats for both ketamine (0.3–3 mg/kg [10–73 ng/ml]) and psilocybin/psilocin (0.05–0.1 mg/kg [7–12 ng/ml]), based on studies which identified these as sub-threshold for the induction of behavioral stereotypies. Tests of efficacy were focused on depression-related endophenotypes of anhedonia, amotivation and cognitive dysfunction using low performing male Long Evans rats trained in two food motivated tasks: a progressive ratio (PR) and serial 5-choice (5-CSRT) task. Both acute doses of ketamine (1–3 mg/kg IP) and psilocybin (0.05–0.1 mg/kg SC) pretreatment increased break point for food (PR task), and improved attentional accuracy and a measure of impulsive action (5-CSRT task). In each case, effect size was modest and largely restricted to test subjects characterized as “low performing”. Furthermore, both drugs showed a similar pattern of effect across both tests. The present studies provide a framework for the future study of ketamine and psilocybin at low doses and plasma exposures, and help to establish the use of these lower concentrations of serotonergic and dissociative hallucinogens both as a valid scientific construct, and as having a therapeutic utility.

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Differences in trait impulsivity do not bias the response to pharmacological drug challenge in the rat five-choice serial reaction time task

Cited by 16 publications

References 56 publications

Interactions between impulsivity and MDPV self‐administration in rats

Interactions between impulsivity and MDPV self‐administration in rats

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

Low Doses of Psilocybin and Ketamine Enhance Motivation and Attention in Poor Performing Rats: Evidence for an Antidepressant Property

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