Effects of atomoxetine and methylphenidate on attention and impulsivity in the 5-choice serial reaction time test

Navarra, Rachel; Graf, Radka; Huang, Yipeng; Logue, Sheree F.; Comery, Thomas A.; Hughes, Zoë A.; Day, Mark L.

doi:10.1016/j.pnpbp.2007.06.017

Cited by 157 publications

(196 citation statements)

References 56 publications

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“…Selective NET inhibitors such as atomoxetine [(3R)-N-methyl-3-(2-methylphenoxy)-3-phenylpropan-1-amine] and reboxetine [(2S)-2-[(S)-(2-ethoxyphenoxy)-phenylmethyl]morpholine], approved for the treatment of attention deficit hyperactivity disorder and MDD, respectively, both decrease premature responding of rodents in the 5-CSRTT (Navarra et al, 2008b;Paterson et al, 2011b;Baarendse and Vanderschuren, 2012;Robinson, 2012). In an analogous manner, selective NET inhibitors reboxetine and (1)-oxaprotiline [(1)-3-(9,10-ethano-9,10-dihydro-9-anthryl)-1-methylamino-2-propanol] increased the reinforcement rate, decreased the response rate, and exerted a cohesive rightward shift in the IRT distribution of rats responding on a DRL 72-second schedule Wong et al, 2000;Dekeyne et al, 2002).…”

Section: Rethinking An Empirical Antidepressant Screenmentioning

confidence: 99%

“…Examination of adequate dose ranges over adequate 5-CSRTT intertrial intervals tends to show beneficial effects of methylphenidate (methyl 2-phenyl-2-piperidin-2-ylacetate) on the accuracy or omissions, although with increased impulsivity (premature responses) at higher doses (Paine et al, 2007;Navarra et al, 2008b;Paterson et al, 2011a;Robinson, 2012). In rats performing on DRL schedules, methylphenidate also tends to increase response rates and exert cohesive leftward shifts in IRT distributions, especially at higher doses (Seiden et al, 1979;Orduña et al, 2009;Andrzejewski et al, 2014).…”

Section: Rethinking An Empirical Antidepressant Screenmentioning

confidence: 99%

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The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs

Marek

Day

Hudzik

2015

Journal of Pharmacology and Experimental Therapeutics

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Cognitive dysfunction may be a core feature of major depressive disorder, including affective processing bias, abnormal response to negative feedback, changes in decision making, and increased impulsivity. Accordingly, a translational medicine paradigm predicts clinical action of novel antidepressants by examining drug-induced changes in affective processing bias. With some exceptions, these concepts have not been systematically applied to preclinical models to test new chemical entities. The purpose of this review is to examine whether an empirically derived behavioral screen for antidepressant drugs may screen for compounds, at least in part, by modulating an impulsive biasing of responding and altered decision making. The differential-reinforcement-of-low-rate (DRL) 72-second schedule is an operant schedule with a documented fidelity for discriminating antidepressant drugs from nonantidepressant drugs. However, a theoretical basis for this empirical relationship has been lacking. Therefore, this review will discuss whether response bias toward impulsive behavior may be a critical screening characteristic of DRL behavior requiring long interresponse times to obtain rewards. This review will compare and contrast DRL behavior with the five-choice serial reaction time task, a test specifically designed for assessing motoric impulsivity, with respect to psychopharmacological testing and the neural basis of distributed macrocircuits underlying these tasks. This comparison suggests that the existing empirical basis for the DRL 72-second schedule as a pharmacological screen for antidepressant drugs is complemented by a novel hypothesis that altering impulsive response bias for rodents trained on this operant schedule is a previously unrecognized theoretical cornerstone for this screening paradigm.

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Section: Rethinking An Empirical Antidepressant Screenmentioning

confidence: 99%

Section: Rethinking An Empirical Antidepressant Screenmentioning

confidence: 99%

The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs

Marek

Day

Hudzik

2015

Journal of Pharmacology and Experimental Therapeutics

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“…Effective ADHD treatments, including methylphenidate, amphetamine and atomoxetine, reduce impulsive behaviour, probably by enhancing response inhibition, in rats (Navarra et al 2008). Some studies evaluate both cognitive and motor function of DA-depleted rats after intracerebral neonatal microinjections of 6-hydroxydopamine (6-OHDA).…”

Section: Animal Models and The ''Network Inhibition Hypothesis'' Of Nmentioning

confidence: 99%

Pathophysiology of NSS in ADHD

Pasini

D’Agati

2009

The World Journal of Biological Psychiatry

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Attention deficit/hyperactivity disorder (ADHD) is the behavioural disorder most commonly diagnosed in childhood. In addition to the main symptoms of inattention, impulsiveness and hyperactivity, neurological soft signs (NSS) are often associated with ADHD. NSS are discrete motor and sensory disorders that cannot be linked to specific cerebral lesions. We review all the scientific contributions on NSS in ADHD. The conclusions support the presence of an alteration in the neural networks for motor control inhibition, at the base of the pathophysiology of NSS in children with ADHD, as well as a possible central role of dopamine in these neural circuits.

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“…To further evaluate the effects of TAK-063 on impulsivity, variable ITI tests were performed. In these tests, rats must maintain attention for variable durations, and that led to an increase in the baseline levels of premature responses (Navarra et al, 2008;Robinson, 2012). Under these conditions, TAK-063 at 0.3 mg/kg p.o.…”

Section: Discussionmentioning

confidence: 99%

“…Another 16 rats were used only for characterization of TAK-063 in variable ITI tests at 6 months of age. On the testing day, a fixed ITI schedule was used with 0.5-second stimuli and 5-second ITI to assess attention, and impulsivity was assessed using a variable ITI schedule with 0.5-second stimuli at 4, 5, 7, or 10 seconds (Navarra et al, 2008;Robinson, 2012). Equal numbers of each of the four ITIs were randomly presented over 100 trials.…”

Section: Methodsmentioning

confidence: 99%

The Phosphodiesterase 10A Selective Inhibitor TAK-063 Improves Cognitive Functions Associated with Schizophrenia in Rodent Models

Shiraishi

Suzuki

Harada

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Cognitive deficits in various domains, including recognition memory, attention, impulsivity, working memory, and executive function, substantially affect functional outcomes in patients with schizophrenia. TAK-063 [1-[2-fluoro-4-(1H-pyrazol-1-yl) phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4 (1H)-one] is a potent and selective phosphodiesterase 10A inhibitor that produces antipsychotic-like effects in rodent models of schizophrenia. We evaluated the effects of TAK-063 on multiple cognitive functions associated with schizophrenia using naïve and drug-perturbed rodents. TAK-063 at 0.1 and 0.3 mg/kg p.o. improved time-dependent memory decay in object recognition in naïve rats. TAK-063 at 0.1 and 0.3 mg/kg p.o. increased accuracy rate, and TAK-063 at 0.3 mg/kg p.o. reduced impulsivity in a five-choice serial reaction time task in naïve rats. N-methyl-D-aspartate receptor antagonists, such as phencyclidine and MK-801 [(5R,10S)-(1)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine], were used to induce working memory deficits relevant to schizophrenia in animals. TAK-063 at 0.3 mg/kg p.o. attenuated both phencyclidine-induced working memory deficits in a Y-maze test in mice and MK-801-induced working memory deficits in an eight-arm radial maze task in rats. An attentional set-shifting task using subchronic phencyclidine-treated rats was used to assess the executive function. TAK-063 at 0.3 mg/kg p.o. reversed cognitive deficits in extradimensional shifts. These findings suggest that TAK-063 has a potential to ameliorate deficits in multiple cognitive domains impaired in schizophrenia.

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Effects of atomoxetine and methylphenidate on attention and impulsivity in the 5-choice serial reaction time test

Cited by 157 publications

References 56 publications

The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs

The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs

Pathophysiology of NSS in ADHD

The Phosphodiesterase 10A Selective Inhibitor TAK-063 Improves Cognitive Functions Associated with Schizophrenia in Rodent Models

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