Marble-burying is enhanced in 3xTg-AD mice, can be reversed by risperidone and it is modulable by handling

Torres–Lista, Virginia; López-Pousa, Secundino

doi:10.1016/j.beproc.2015.05.001

Cited by 29 publications

(44 citation statements)

References 27 publications

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“…Indeed, this idea is supported by the delineation of hoarding disorder in DSM-5 (Morein-Zamir et al, 2014). Moreover, a recent study (Torres-Lista et al, 2015) demonstrated that only the number of completely buried, and not horizontally displaced or partly buried, marbles positively correlated with increased anxiety in the open-field test, supporting our view that HBB may be related to a different neuropsychological construct than is IBB.…”

Section: Discussionsupporting

confidence: 84%

“…Furthermore, we identified a different withinspecies burying phenotype (HBB), displayed by a small minority of deer mice, that will require further investigation. Burying behavior is a natural phenomenon inherent to most rodent species, and requires experimental and methodological manipulation, such as pretest restraint (Kedia & Chattarji, 2014) or correlations with other behavioral tests (Londei et al, 1998;Torres-Lista et al, 2015), to be a useful screening tool for either anxiety or compulsivity. Using a known OCD translational model has identified the inherent shortcomings of the MB test for obsessive-compulsive behavior, although this finding should be confirmed in other translational models (e.g., Joel & Avisar, 2001;Szechtman et al, 2001), as well as in the promising range of genetic models currently available (Berridge, Aldridge, Houchard, & Zhuang, 2005;Chou-Green, Holscher, Dallman, & Akana, 2003;Shanahan et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

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Of mice and marbles: Novel perspectives on burying behavior as a screening test for psychiatric illness

Wolmarans

Stein

Harvey

2016

Cogn Affect Behav Neurosci

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Burying forms part of the normal behavioral routine of rodents, although its expression is species-specific. However, it has been suggested that aberrant burying behavior, of which marble-burying (MB) is an example, may represent neophobic and/or compulsive-like behavior. In the present investigation, we assessed MB in an established animal model of obsessive-compulsive disorder (OCD)-namely, spontaneous stereotypy in the deer mouse-to establish whether high (H) stereotypy is associated with neophobia and/or another compulsive endophenotype, i.e. MB, as compared to nonstereotypical (N) controls. A three-trial, one-zone MB test was performed over three consecutive evenings both before and after chronic treatment with high-dose (50 mg/kg/ day) oral escitalopram. Neophobia was measured via the number of marbles buried during the first pre-and posttreatment MB trials, and compulsive-like behavior via the number of marbles buried over all pre-and posttreatment MB trials. The data from the present study support earlier findings that burying is a normal behavioral routine (inherent burying behavior, IBB) that is expressed by all deer mice, irrespective of stereotypical cohort, and is not associated with either neophobia or compulsiveness. Indeed, chronic escitalopram treatment, which is similarly effective in treating clinical anxiety and OCD, as well as in attenuating H behavior, failed to influence IBB. Although 11 % of the animals presented with a unique burying endophenotype (high burying behavior), escitalopram also failed to attenuate said behavior, necessitating further investigation as to its relevance. In conclusion, MB cannot be regarded as a measure of anxiety-like or compulsive behavior in the deer mouse model of OCD.Keywords Marble-burying . Obsessive-compulsive disorder . Neophobia . Deer mouse . Animal model . Escitalopram Burying, burrowing, and digging form part of the normal behavioral repertoire of rodents, in both the wild and the laboratory (Deacon, 2006;Smithers, 1983). These strain-specific behaviors are mostly aimed at searching for food, burying both noxious and harmless objects, and building adequate nurseries capable of protecting individuals against predators and providing suitable environments to breed (Smithers, 1983). Evidently, burying and digging are expressed in relatively nonanxiogenic scenarios (e.g., nesting, hoarding, foraging), as well as under anxiogenic circumstances (e.g., burying of noxious objects, confronting predators).Defensive burying (Pinel & Treit, 1978) can be defined as the process of moving loose bedding material vertically upward and over potentially harmful stimuli or sources of aversive stimulation (e.g., a shock prod). Due to the stressprovoking nature of an electric shock, defensive burying has been used as a measure of avoidance-dependent anxiety in a Electronic supplementary material The online version of this article

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Of mice and marbles: Novel perspectives on burying behavior as a screening test for psychiatric illness

Wolmarans

Stein

Harvey

2016

Cogn Affect Behav Neurosci

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“…Another common innate phenotypic test performed on mouse models is marble burying, although its translational validity has been under debate [43]. Some studies have suggested marble burying could be a neophobic response [44], repetitive/compulsive [29,45], or just a normal behavioral routine of inherent burying behavior [46]. Decreased nesting and marble burying were also observed in a Fragile-X mouse model [47].…”

Section: Discussionmentioning

confidence: 99%

Characterization of a gene-trap knockout mouse model ofScn2aencoding voltage-gated sodium channel Nav1.2

Eaton

Zhang

et al. 2020

Preprint

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Recent large-scale genomic studies have revealed SCN2A as one of the most frequently mutated gene in patients with neurodevelopmental disorders including autism spectrum disorder and intellectual disability. SCN2A encodes for voltage-gated sodium channel isoform 1.2 (Nav1.2), which is mainly expressed in the central nervous system and responsible for the propagation of neuronal action potentials. Homozygous knockout (null) of Scn2a is perinatal lethal, whereas heterozygous knockout of Scn2a results in mild behavior abnormalities. To achieve a more substantial, but not complete, reduction of Scn2a expression, we characterized a Scn2a deficient mouse model using a targeted gene trap knockout (gtKO) strategy to recapitulate loss-of-function SCN2A disorders. This model produces viable homozygous mice (Scn2a gtKO/gtKO ) that can survive to adulthood, with markedly low but detectable Nav1.2 expression. Although Scn2a gtKO/gtKO adult mice possess normal olfactory, taste, hearing, and mechanical sensitivity, they have decreased thermal and cold tolerance. Innate behaviors are profoundly impaired including impaired nesting, marble burying, and mating. These mice also have increased food and water intake with subsequent increases in fecal excretion of more but smaller fecal boli. This novel Scn2a gene trap knockout mouse thus provides a unique model to study pathophysiology associated with Scn2a deficiency.

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“…Briefly, the test involves the placement of any number of marbles (usually between 4 and 25, depending on the zone configuration of the marble-burying arena; see paragraphs 5.2 and 5.5; Çalişkan et al, 2017) gently onto the surface of a layer of bedding material (normally no thicker than 5 cm). However, whereas Broekkamp et al (1986) placed the marbles in close contact with one another centrally in the cage, most recent investigations have employed an experimental configuration in which marbles were spaced evenly throughout the arena (one-zone; 1Z; Egashira et al, 2018;Gawali et al, 2016;Millan et al, 2002) or in one section of the arena only (two-zone; 2Z; Gyertyán, 1995;Nicolas et al, 2006;Njung'e & Handley, 1991b;Torres-Lista et al, 2015). Occasionally, marbles are placed around the perimeter of the burying cage, as well (Chaki et al, 2003;Taylor et al, 2017;Young, Batkai, Dukat, & Glennon, 2006), resembling another example of a two-zone setup.…”

Section: A Methodological Review Of the Mbtmentioning

confidence: 99%

“…Chourbaji, 2017;Uday, Pravinkumar, Manish, & Sudhir, 2007;Umathe, Manna, & Jain, 2012) drug action. It is also used as a model to characterize and quantify the purported behavioral manifestations of neuropsychological constructs related to, inter alia, posttraumatic stress disorder (PTSD; Kedia & Chattarji, 2014) and Alzheimer's disease (Torres-Lista, López-Pousa, & Giménez-Llort, 2015). However, the marble-burying test (MBT) is characterized by variable responses to a range of pharmacological compounds administered both acutely and chronically (Millan, Girardon, Mullot, Brocco, & Dekeyne, 2002;Sugimoto, Tagawa, Kobayashi, Hotta, & Yamada, 2007;Taylor et al, 2017;Umathe et al, 2012), and little consensus exists regarding the specific methodology to be followed in its execution (Çalişkan et al, 2017), even when the test is applied with respect to a specific condition (Jimenez-Gomez, Osentoski, & Woods, 2011;Sugimoto et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

A critical inquiry into marble-burying as a preclinical screening paradigm of relevance for anxiety and obsessive–compulsive disorder: Mapping the way forward

Brouwer

Fick

Harvey

et al. 2018

Cogn Affect Behav Neurosci

118

111

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Rodent marble-burying behavior in the marble-burying test (MBT) is employed as a model or measure to study anxiety-and compulsive-like behaviors or anxiolytic and anticompulsive drug action. However, the test responds variably to a range of pharmacological interventions, and little consensus exists regarding specific methodologies for its execution. Regardless, the test is widely applied to investigate the effects of pharmacological, genetic, and behavioral manipulations on purported behaviors related to the said neuropsychiatric constructs. Therefore, in the present review we attempt to expound the collective translational significance of the MBT. We do this by (1) reviewing burying behavior as a natural behavioral phenotype, (2) highlighting key aspects of anxiety and obsessive-compulsive disorder from a translational perspective, (3) reviewing the history and proof of concept of the MBT, (4) critically appraising potential methodological confounds in execution of the MBT, and (5) dissecting responses of the MBT to various pharmacological interventions. We conclude by underlining that the collective translational value of the MBT will be strengthened by contextually valid experimental designs and objective reporting of data.

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Marble-burying is enhanced in 3xTg-AD mice, can be reversed by risperidone and it is modulable by handling

Cited by 29 publications

References 27 publications

Of mice and marbles: Novel perspectives on burying behavior as a screening test for psychiatric illness

Of mice and marbles: Novel perspectives on burying behavior as a screening test for psychiatric illness

Characterization of a gene-trap knockout mouse model ofScn2aencoding voltage-gated sodium channel Nav1.2

A critical inquiry into marble-burying as a preclinical screening paradigm of relevance for anxiety and obsessive–compulsive disorder: Mapping the way forward

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