Evidence map›Paper›PMID 28251298›Full record

ArticlePsychopharmacology2017

Perseveration in a spatial-discrimination serial reversal learning task is differentially affected by MAO-A and MAO-B inhibition and associated with reduced anxiety and peripheral serotonin levels.

Peter Zhukovsky, Johan Alsiö, Bianca Jupp, Jing Xia, Chiara Giuliano, Lucy Jenner, Jessica Griffiths, Errin Riley, Sajeed Ali, Angela C Roberts and 2 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Psychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.6field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 24 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 3 countries.

Peter ZhukovskyBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Johan AlsiöBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Bianca JuppBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Jing XiaBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Chiara GiulianoBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Lucy JennerBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Jessica GriffithsBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Errin RileyBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Sajeed AliBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Angela C RobertsBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Trevor W RobbinsBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Jeffrey W DalleyBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK. jwd20@cam.ac.uk.
University of Cambridge · GBFlorey Institute of Neuroscience and Mental Health · AU

Funding

Medical Research Council G0001354Medical Research Council G0701500Medical Research Council G1000183Medical Research Council G9536855Wellcome Trust 093875/Z/10/ZWellcome Trust 106431/Z/14/Z
6 · The paper itself

Abstract

rationaleImpairments in behavioral flexibility lie at the core of anxiety and obsessive-compulsive disorders. Few studies, however, have investigated the neural substrates of natural variation in behavioral flexibility and whether inflexible behavior is linked to anxiety and peripheral markers of stress and monoamine function.

objectiveThe objective of the study was to investigate peripheral and central markers associated with perseverative behavior on a spatial-discrimination serial reversal learning task.

methodsRats were trained on a reversal learning task prior to blood sampling, anxiety assessment, and the behavioral evaluation of selective monoamine oxidase-A (MAO-A) and MAO-B inhibitors, which block the degradation of serotonin (5-HT), dopamine (DA), and noradrenaline (NA).

resultsPerseveration correlated positively with 5-HT levels in blood plasma and inversely with trait anxiety, as measured on the elevated plus maze. No significant relationships were found between perseveration and the stress hormone corticosterone or the 5-HT precursor tryptophan. Reversal learning was significantly improved by systemic administration of the MAO-A inhibitor moclobemide but not by the MAO-B inhibitor lazabemide. Moclobemide also increased latencies to initiate a new trial following an incorrect response suggesting a possible role in modulating behavioral inhibition to negative feedback. MAO-A but not MAO-B inhibition resulted in pronounced increases in 5-HT and NA content in the orbitofrontal cortex and dorsal raphé nuclei and increased 5-HT and DA content in the basolateral amygdala and dorsomedial striatum.

conclusionsThese findings indicate that central and peripheral monoaminergic mechanisms underlie inter-individual variation in behavioral flexibility, which overlaps with trait anxiety and depends on functional MAO-A activity.

Indexed as

AnimalsAnxietyDiscrimination LearningDorsal Raphe NucleusDose-Response Relationship, DrugMaleMaze LearningMonoamine OxidaseMonoamine Oxidase InhibitorsPrefrontal CortexRatsReversal LearningSerial LearningSerotoninSpatial BehaviorMonoamine OxidaseMonoamine Oxidase InhibitorsSerotoninBasolateral amygdalaBehavioral flexibilityEndophenotypeLazabemideMoclobemideOrbitofrontal cortexStriatum

Identifiers

PMID28251298
PMCPMC5420387
OpenAlexW2594529918

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.