Aligning physiology with psychology: Translational neuroscience in neuropsychiatric drug discovery

McArthur, Robert A.

doi:10.1016/j.neubiorev.2017.02.004

Cited by 40 publications

(11 citation statements)

References 360 publications

(407 reference statements)

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“…The adoption of tests that can be used across species from the preclinical to the clinical setting is widely recognized as a logical approach to improve translational reliability (e.g. Pangalos et al, 2007;Day et al, 2008;Markou et al, 2009;Goetghebeur and Swartz, 2016;McArthur, 2017;Robbins, 2017). Attention is commonly measured using the 5-CSRTT, a test that can be conducted in rodents, primates and humans (Robbins, 2002;Bari et al, 2008;Higgins and Silenieks, 2017).…”

Section: Rationale For Test Selectionmentioning

confidence: 99%

“…One reaction to this view has been to place emphasis on translational research where animal tests are designed to align closely to those conducted in humans, and conversely to design early phase human tests taking features from existing animal tests. A closer correspondence between preclinical and clinical measures should enhance predictability and promote translation back and forth between animal and human studies (Pangalos et al, 2007;Conn and Roth, 2008;Day et al, 2008;Miczek and de Wit, 2008;Markou et al, 2009;Goetghebeur and Swartz, 2016;McArthur, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…These endophenotypes include constructs such as attention, impulsivity, working memory, motivation which can be objectively measured in animals using appropriate tests and experimental conditions. Thus complex clinical disorders can be fractionated into discrete symptom clusters which may be more amenable to translational research and treatment (Pangalos et al, 2007;Day et al, 2008;Miczek and de Wit, 2008;Markou et al, 2009;McArthur, 2017).…”

Section: Introductionmentioning

confidence: 99%

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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: Rationale For Test Selectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Potential neuropsychiatric drugs show a large amount of attrition from phase I trials to approval. Of the 60% of compounds that progress to phase II trials, a third will progress to phase III, but less than half of these will be reviewed by regulatory bodies and only 8.2% will be approved (McArthur, 2017).…”

Section: Improving Ability To Evidence Efficacy Of New Treatmentsmentioning

confidence: 99%

Why we need more research into the placebo response in psychiatry

et al. 2020

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Placebos are not inert, but exert measurable biological effects. The placebo response in psychiatric illness is important and clinically relevant, but remains poorly understood. In this paper, we review current knowledge about the placebo response in psychiatric medicine and identify research directions for the future. We argue that more research is needed into the placebo response in psychiatric medicine for three broad reasons. First, awareness of factors that cause placebo response, for whom, and when, within clinical trials will allow us to better evidence efficacy of new treatments. Second, by understanding how placebo mechanisms operate in the clinic, we can take advantage of these to optimise the effects of current treatments. Finally, exploring the biological mechanisms of placebo effects might reveal tractable targets for novel treatment development.

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“…Neuroimaging evidences can help us understand psychological and psychopathological phenomena to better develop our knowledge of models and treatment procedures (Allen et al, 2017; Aybek and Vuilleumier, 2017; Mcarthur, 2017; Warren et al, 2017). …”

Section: Introductionmentioning

confidence: 99%

New and Old Adventures of Clinical Health Psychology in the Twenty-First Century: Standing on the Shoulders of Giants

Castelnuovo

2017

Front. Psychol.

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Aligning physiology with psychology: Translational neuroscience in neuropsychiatric drug discovery

Cited by 40 publications

References 360 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

Why we need more research into the placebo response in psychiatry

New and Old Adventures of Clinical Health Psychology in the Twenty-First Century: Standing on the Shoulders of Giants

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