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 levelsReport as inadecuate




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 - Download this document for free, or read online. Document in PDF available to download.

Psychopharmacology

, Volume 234, Issue 9–10, pp 1557–1571

First Online: 02 March 2017Received: 10 September 2016Accepted: 15 February 2017DOI: 10.1007-s00213-017-4569-x

Cite this article as: Zhukovsky, P., Alsiö, J., Jupp, B. et al. Psychopharmacology 2017 234: 1557. doi:10.1007-s00213-017-4569-x

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.

Key wordsBehavioral flexibility Moclobemide Lazabemide Endophenotype Orbitofrontal cortex Basolateral amygdala Striatum 



Author: Peter Zhukovsky - Johan Alsiö - Bianca Jupp - Jing Xia - Chiara Guiliano - Lucy Jenner - Jessica Griffiths - Errin Riley

Source: https://link.springer.com/







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