Erratum to: 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

ABSTRACT Much evidence suggests that reversal learning is mediated by cortico-striatal circuitries with the orbitofrontal cortex (OFC) playing a prominent role. The OFC is a functionally heterogeneous region, but potential differential roles of lateral (lOFC) and medial (mOFC) portions in visual reversal learning have yet to be determined. We investigated the effects of pharmacological inactivation of mOFC and lOFC on a deterministic serial visual reversal learning task for rats. For reference, we also targeted other areas previously implicated in reversal learning: prelimbic (PrL) and infralimbic (IL) prefrontal cortex, and basolateral amygdala (BLA). Inactivating mOFC and lOFC produced opposite effects; lOFC impairing, and mOFC improving, performance in the early, perseverative phase specifically. Additionally, mOFC inactivation enhanced negative feedback sensitivity, while lOFC inactivation diminished feedback sensitivity in general. mOFC and lOFC inactivation also affected novel visual discrimination learning differently; lOFC inactivation paradoxically improved learning, and mOFC inactivation had no effect. We also observed dissociable roles of the OFC and the IL/PrL. Whereas the OFC inactivation affected only perseveration, IL/PrL inactivation improved learning overall. BLA inactivation did not affect perseveration, but improved the late phase of reversal learning. These results support opponent roles of the rodent mOFC and lOFC in deterministic visual reversal learning.

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Markers of Serotonergic Function in the Orbitofrontal Cortex and Dorsal Raphé Nucleus Predict Individual Variation in Spatial-Discrimination Serial Reversal Learning

Neuropsychopharmacology ◽

10.1038/npp.2014.335 ◽

2015 ◽

Vol 40 (7) ◽

pp. 1619-1630 ◽

Cited By ~ 37

Author(s):

Rebecca L Barlow ◽

Johan Alsiö ◽

Bianca Jupp ◽

Rebecca Rabinovich ◽

Saurav Shrestha ◽

...

Keyword(s):

Reversal Learning ◽

Orbitofrontal Cortex ◽

Individual Variation ◽

Dorsal Raphe Nucleus ◽

Dorsal Raphe ◽

Raphe Nucleus ◽

Spatial Discrimination ◽

Serotonergic Function ◽

Dorsal Raphé ◽

Serial Reversal

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The performance of cleaner wrasse, Labroides dimidiatus, in a reversal learning task varies across experimental paradigms

10.7287/peerj.preprints.3406v1 ◽

2017 ◽

Author(s):

Fanny Marcadier ◽

Sandra A Binning ◽

Sharon Wismer ◽

Océane Krattinger ◽

Fausto Quatttrini ◽

...

Keyword(s):

Cognitive Performance ◽

Reversal Learning ◽

Cognitive Abilities ◽

Learning Task ◽

Performance Outcomes ◽

Cognitive Testing ◽

Spatial Discrimination ◽

Labroides Dimidiatus ◽

Set Up ◽

Experimental Treatments

Testing cognitive performance in controlled laboratory experiments is a powerful tool for understanding the extent and evolution of cognitive abilities in non-human animals. However, cognitive testing is prone to a number of potential biases, which, if unnoticed or unaccounted for, may affect the conclusions drawn. We examined whether slight modifications to the experimental procedure and apparatus used in a spatial discrimination and reversal learning task affected performance outcomes in the bluestreak cleaner wrasse, Labroides dimidiatus (hereafter ‘cleaners’). Using two-alternative forced choice tests, fish had to learn to associate a food reward with a side (left or right) in their holding aquarium. Individuals were tested in one of four experimental treatments that differed slightly in procedure and/or physical set-up. Cleaners from all four treatment groups were equally able to solve the initial spatial discrimination test. However, groups differed in their ability to solve the reversal learning task: no individuals solved the reversal task when tested in small tanks with a transparent partition separating the two options, whereas over 50% of individuals solved the task when performed in a larger tank, or with an opaque partition. These results clearly show that seemingly insignificant details to the experimental set-up matter when testing cognitive performance, and might significantly influence the outcome of experiments. When designing the methodology for comparative cognitive tests, care should be taken to ensure that all groups understand and can respond to the relevant cue to avoid misinterpretations.

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The performance of cleaner wrasse, Labroides dimidiatus, in a reversal learning task varies across experimental paradigms

10.7287/peerj.preprints.3406 ◽

2017 ◽

Author(s):

Fanny Marcadier ◽

Sandra A Binning ◽

Sharon Wismer ◽

Océane Krattinger ◽

Fausto Quatttrini ◽

...

Keyword(s):

Cognitive Performance ◽

Reversal Learning ◽

Cognitive Abilities ◽

Learning Task ◽

Performance Outcomes ◽

Cognitive Testing ◽

Spatial Discrimination ◽

Labroides Dimidiatus ◽

Set Up ◽

Experimental Treatments

Testing cognitive performance in controlled laboratory experiments is a powerful tool for understanding the extent and evolution of cognitive abilities in non-human animals. However, cognitive testing is prone to a number of potential biases, which, if unnoticed or unaccounted for, may affect the conclusions drawn. We examined whether slight modifications to the experimental procedure and apparatus used in a spatial discrimination and reversal learning task affected performance outcomes in the bluestreak cleaner wrasse, Labroides dimidiatus (hereafter ‘cleaners’). Using two-alternative forced choice tests, fish had to learn to associate a food reward with a side (left or right) in their holding aquarium. Individuals were tested in one of four experimental treatments that differed slightly in procedure and/or physical set-up. Cleaners from all four treatment groups were equally able to solve the initial spatial discrimination test. However, groups differed in their ability to solve the reversal learning task: no individuals solved the reversal task when tested in small tanks with a transparent partition separating the two options, whereas over 50% of individuals solved the task when performed in a larger tank, or with an opaque partition. These results clearly show that seemingly insignificant details to the experimental set-up matter when testing cognitive performance, and might significantly influence the outcome of experiments. When designing the methodology for comparative cognitive tests, care should be taken to ensure that all groups understand and can respond to the relevant cue to avoid misinterpretations.

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Inhibition of Butyrylcholinesterase and Human Monoamine Oxidase-B by the Coumarin Glycyrol and Liquiritigenin Isolated from Glycyrrhiza uralensis

Molecules ◽

10.3390/molecules25173896 ◽

2020 ◽

Vol 25 (17) ◽

pp. 3896

Author(s):

Geum Seok Jeong ◽

Myung-Gyun Kang ◽

Joon Yeop Lee ◽

Sang Ryong Lee ◽

Daeui Park ◽

...

Keyword(s):

Monoamine Oxidase ◽

Binding Affinity ◽

Competitive Inhibitor ◽

Glycyrrhiza Uralensis ◽

Form Hydrogen Bond ◽

Docking Simulations ◽

Mao B ◽

Mao A ◽

Ic50 Values ◽

Noncompetitive Inhibitor

Eight compounds were isolated from the roots of Glycyrrhiza uralensis and tested for cholinesterase (ChE) and monoamine oxidase (MAO) inhibitory activities. The coumarin glycyrol (GC) effectively inhibited butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) with IC50 values of 7.22 and 14.77 µM, respectively, and also moderately inhibited MAO-B (29.48 µM). Six of the other seven compounds only weakly inhibited AChE and BChE, whereas liquiritin apioside moderately inhibited AChE (IC50 = 36.68 µM). Liquiritigenin (LG) potently inhibited MAO-B (IC50 = 0.098 µM) and MAO-A (IC50 = 0.27 µM), and liquiritin, a glycoside of LG, weakly inhibited MAO-B (>40 µM). GC was a reversible, noncompetitive inhibitor of BChE with a Ki value of 4.47 µM, and LG was a reversible competitive inhibitor of MAO-B with a Ki value of 0.024 µM. Docking simulations showed that the binding affinity of GC for BChE (−7.8 kcal/mol) was greater than its affinity for AChE (−7.1 kcal/mol), and suggested that GC interacted with BChE at Thr284 and Val288 by hydrogen bonds (distances: 2.42 and 1.92 Å, respectively) beyond the ligand binding site of BChE, but that GC did not form hydrogen bond with AChE. The binding affinity of LG for MAO-B (−8.8 kcal/mol) was greater than its affinity for MAO-A (−7.9 kcal/mol). These findings suggest GC and LG should be considered promising compounds for the treatment of Alzheimer’s disease with multi-targeting activities.

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Development of Monoamine Oxidase and Aldehyde Dehydrogenase in Reaggregating Cultures of Fetal Rat Brain Cells

Alternatives to Laboratory Animals ◽

10.1177/026119298901600313 ◽

1989 ◽

Vol 16 (3) ◽

pp. 281-286

Author(s):

Olof Tottmar ◽

Maria Söderbäck ◽

Anders Aspberg

Keyword(s):

Monoamine Oxidase ◽

Rat Brain ◽

Aldehyde Dehydrogenase ◽

Brain Cells ◽

Mao B ◽

Adult Rat ◽

Fetal Rat ◽

Adult Rat Brain ◽

Mao A ◽

Fetal Rat Brain

The development of monoamine oxidase (MAO) and aldehyde dehydrogenase (ALDH) in reaggregation cultures of fetal rat brain cells was compared with that of enzymatic markers for glial and neuronal cells. Only MAO-A was detected in the cultures during the first week, but, during the following three weeks, the activity of MAO-B increased more rapidly than that of MAO-A. The ratio MAO-A/MAO-B in four-week aggregates was close to that found in the adult rat brain. The activity of ALDH started to increase rapidly after 15 days, and the developmental pattern was intermediate to those of the glial and neuronal markers. The activity after four weeks was close to that found in the adult rat brain. Epidermal growth factor (EGF) caused a slight decrease in the activities of the low-Km ALDH (after four weeks) and the neuronal marker, choline acetyltransferase (after two weeks), whereas the other markers were not affected. By contrast, the activities of MAO-A and MAO-B were greatly increased during almost the entire culture period. It is suggested that this effect of EGF was the result of increased mitotic activity and/or biochemical differentiation of other cell types present in the cell aggregates, e.g. capillary endothelial cells.

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In Vitro,In Vivo, and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00431-13 ◽

2013 ◽

Vol 57 (7) ◽

pp. 3060-3066 ◽

Cited By ~ 61

Author(s):

S. Flanagan ◽

K. Bartizal ◽

S. L. Minassian ◽

E. Fang ◽

P. Prokocimer

Keyword(s):

Blood Pressure ◽

Monoamine Oxidase ◽

Clinical Research ◽

Systolic Blood Pressure ◽

Clinical Studies ◽

Geometric Mean ◽

Interaction Study ◽

Mao B ◽

Mao A

ABSTRACTTedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions.In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-Bin vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered atwww.clinicaltrials.govas NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459 (pseudoephedrine interaction study conducted at Vince and Associates Clinical Research, Overland Park, KS).

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Environmental enrichment enhances cognitive flexibility in C57BL/6 mice on a touchscreen reversal learning task

Neuropharmacology ◽

10.1016/j.neuropharm.2017.02.009 ◽

2017 ◽

Vol 117 ◽

pp. 219-226 ◽

Cited By ~ 22

Author(s):

Ariel Zeleznikow-Johnston ◽

Emma L. Burrows ◽

Thibault Renoir ◽

Anthony J. Hannan

Keyword(s):

Cognitive Flexibility ◽

Reversal Learning ◽

Environmental Enrichment ◽

Learning Task

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Styrene Impairs Serial Spatial Reversal Learning in Rats

Journal of the American College of Toxicology ◽

10.3109/10915819409140600 ◽

1994 ◽

Vol 13 (4) ◽

pp. 279-300 ◽

Cited By ~ 2

Author(s):

Philip J. Bushnell

Keyword(s):

Total Dose ◽

Reversal Learning ◽

Positive Response ◽

Corn Oil ◽

Behavioral Effect ◽

Food Delivery ◽

Reversal Training ◽

Factors Affecting ◽

Styrene Exposure ◽

Serial Reversal

To evaluate the effects of styrene exposure on learning, adult male Long-Evans rats learned repeated reversals of a spatial discrimination task. Styrene monomer (50% vol/vol in corn oil) was administered by gavage to groups of eight rats at 500 mg/kg/day, 5 days/week, for 8 weeks in Experiments (Exps) I and II (total dose = 20.0 g/kg) or for 1,3,5, or 8 weeks in Exp III (total dose = 2.5, 7.5, 12.5, or 20.0 g/kg). Control rats received corn oil vehicle for 8 weeks. Reversal training began 8 (Exp I), 10 (Exp II), or 32 (Exp III) weeks after termination of dosing. In Exp I, an instrumental (IN) schedule was used, under which rats received food after each presentation of a “positive” response lever (S+ ) only if they had made at least one response during that presentation of S+. In Exps II and III, an automaintenance (AU) schedule was used, under which rats received food after every presentation of S+, regardless of responding. In all experiments, a second manipulandum (S°) was presented randomly in time with respect to S + and food delivery. A discrimination ratio (DR) was calculated as the proportion of total responses on S+ in each block of 10 trials. A reversal involved switching the reward values of S+ and S°. Serial reversal learning was quantified in terms of trials to criterion. Reversal learning improved similarly in control and treated rats trained under the IN schedule, whereas treated rats trained under the AU schedule failed to improve as much as controls. Reversal learning of some styrene-treated AU rats in Exp III continued to be impaired for > 1 year after treatment. Increased responding on S° featured prominently in the behavioral effect of styrene. An IN schedule requiring suppression of S° responses for food in Exp III revealed a clear deficit in rats exposed to styrene. Not all treated rats were affected by styrene; nevertheless, changes in the affected individuals were as large as those previously observed after trimethyltin-induced lesions of the CNS. The incidence of impairment was not related to the total dose of styrene given, suggesting the action of other, undetermined factors affecting individual sensitivity to styrene.

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