Evidence map›Paper›PMID 25567428›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015

Markers of serotonergic function in the orbitofrontal cortex and dorsal raphé nucleus predict individual variation in spatial-discrimination serial reversal learning.

Rebecca L Barlow, Johan Alsiö, Bianca Jupp, Rebecca Rabinovich, Saurav Shrestha, Angela C Roberts, Trevor W Robbins, Jeffrey W Dalley

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 6% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.

  1. Cognitive Inflexibility in OCD and Related Disorders.Current topics in behavioral neurosciences · 2021
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  16. Increasing Central Serotonin with 5-hydroxytryptophan Disrupts the Inhibition of Social Gaze in Nonhuman Primates.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Rebecca L BarlowBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Johan Alsiö1] Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK [2] Department of Neuroscience, University of Uppsala, Uppsala, Sweden.
Bianca Jupp1] Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK [2] Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
Rebecca RabinovichBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Saurav ShresthaNIMH, IRP, Bethesda, MD, USA.
Angela C Roberts1] Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK [2] Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
Trevor W RobbinsBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Jeffrey W Dalley1] Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK [2] Department of Psychiatry, University of Cambridge, Cambridge, UK.
University of Cambridge · GB

Funding

Medical Research Council G0001354Medical Research Council G0701500Medical Research Council G0802729Medical Research Council G1000183Medical Research Council G1000183BMedical Research Council G1002231Medical Research Council MR/J012084/1Wellcome Trust 089589/Z/09/ZWellcome Trust 093875Wellcome Trust 093875/Z/10/ZWellcome Trust 104631
6 · The paper itself

Abstract

Dysfunction of the orbitofrontal cortex (OFC) impairs the ability of individuals to flexibly adapt behavior to changing stimulus-reward (S-R) contingencies. Impaired flexibility also results from interventions that alter serotonin (5-HT) and dopamine (DA) transmission in the OFC and dorsomedial striatum (DMS). However, it is unclear whether similar mechanisms underpin naturally occurring variations in behavioral flexibility. In the present study, we used a spatial-discrimination serial reversal procedure to investigate interindividual variability in behavioral flexibility in rats. We show that flexibility on this task is improved following systemic administration of the 5-HT reuptake inhibitor citalopram and by low doses of the DA reuptake inhibitor GBR12909. Rats in the upper quintile of the distribution of perseverative responses during repeated S-R reversals showed significantly reduced levels of the 5-HT metabolite, 5-hydroxy-indoleacetic acid, in the OFC. Additionally, 5-HT2A receptor binding in the OFC of mid- and high-quintile rats was significantly reduced compared with rats in the low-quintile group. These perturbations were accompanied by an increase in the expression of monoamine oxidase-A (MAO-A) and MAO-B in the lateral OFC and by a decrease in the expression of MAO-A, MAO-B, and tryptophan hydroxylase in the dorsal raphé nucleus of highly perseverative rats. We found no evidence of significant differences in markers of DA and 5-HT function in the DMS or MAO expression in the ventral tegmental area of low- vs high-perseverative rats. These findings indicate that diminished serotonergic tone in the OFC may be an endophenotype that predisposes to behavioral inflexibility and other forms of compulsive behavior.

Indexed as

AnimalsCitalopramConditioning, OperantDiscrimination, PsychologicalDorsal Raphe NucleusDose-Response Relationship, DrugGene ExpressionMaleMonoamine OxidasePiperazinesPrefrontal CortexProtein BindingRatsReinforcement, PsychologyReversal LearningRNA, MessengerCitalopramMonoamine OxidasePiperazinesRNA, MessengerSelective Serotonin Reuptake InhibitorsSerotonintph2 protein, ratTryptophan Hydroxylasevanoxerine

Identifiers

PMID25567428
PMCPMC4915245
OpenAlexW2034531314

What OpenQuestion holds

Textmetadata
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.