Effects of mood stabilizers on marble-burying behavior in mice

Egashira, Nobuaki; Abe, Moe; Shirakawa, Atsunori; Niki, Tomiko; Mishima, Kenichi; Iwasaki, Katsunori; Oishi, Ryozo; Fujiwara, Michihiro

doi:10.1007/s00213-012-2904-9

Cited by 18 publications

(20 citation statements)

References 67 publications

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“…Meanwhile, Usp46 -deficient mice exhibited significantly higher scores than WT mice in the marble burying test. Marble burying behavior is thought to be a pharmacological model for obsessive-compulsive disorder [29], and this behavior is also regulated by the GABAergic system [30]. Taken together, these results suggest that Usp46 controls a broad range of behavioral phenotypes, and presently, it is difficult to extrapolate the behavioral phenotype of Usp46- deficient mice to any specific mental disorders.…”

Section: Discussionmentioning

confidence: 99%

Behavioral Characteristics of Ubiquitin-Specific Peptidase 46-Deficient Mice

Imai

Kano²,

Nonoyama³

et al. 2013

PLoS ONE

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We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST) and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92), and mice with this mutation (MT mice), as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA) receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT) or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system.

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Section: Discussionmentioning

confidence: 99%

Behavioral Characteristics of Ubiquitin-Specific Peptidase 46-Deficient Mice

Imai

Kano²,

Nonoyama³

et al. 2013

PLoS ONE

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“…In fact, it has been shown that marble-burying persists over repeated exposure, even when avoidance of the marbles is possible and after animals have been habituated to the presence of marbles in their home cage environments for extended periods (Njung'e & Handley, 1991b;Thomas et al, 2009). Moreover, the facts that marble-burying correlates poorly with the outcomes of other classical experimental tests of anxiety (Sanathara et al, 2018;Savy et al, 2015;Thomas et al, 2009; although see also Greene-Schloesser et al, 2011) and that it is subject to significant between-strain variation (Angoa-Pérez, Kane, Briggs, Francescutti, & Kuhn, 2013;Egashira et al, 2013;Nicolas et al, 2006;Thomas et al, 2009) further suggest that marble-burying as it is normally carried out in the lab-that is, not based on individual differences in behavior, but rather to characterize group differences in supposed abnormal burying behavior, mostly following drug intervention-represents an inherent, rather than a neophobic or anxiety-related, behavioral phenotype. As such, the MBT has since been employed to model the purported behavioral manifestations of OCD-that is, seemingly purposeless repetition Gaikwad, Parle, Kumar, & Gaikwad, 2010;Iijima, Kurosu, & Chaki, 2010;Taylor et al, 2017;Umathe, Bhutada, Dixit, & Shende, 2008;Umathe et al, 2012); in most cases, however, this approach is also unjustified, as will be explained.…”

Section: The Mbt: a Brief History And Proof Of Conceptmentioning

confidence: 99%

“…Investigations into MBA that have also reported results from locomotor assessments have employed several approaches, including separate analyses of LMA (Krass et al, 2010;Millan et al, 2002;Saadat et al, 2006) and simultaneous recording of marble-burying and LMA (Egashira et al, 2018;Jimenez-Gomez et al, 2011;Matsushita et al, 2005;Nicolas et al, 2006). Furthermore, LMA assessments may employ either the same subjects tested for marble-burying behavior (Egashira et al, 2013;Schneider & Popik, 2007;Umathe, Vaghasiya, Jain, & Dixit, 2009) or a separate group exposed to treatment regimens analogous to that of the group tested for burying behavior (Gaikwad et al, 2010;Saadat et al, 2006;Uday et al, 2007). Considering that marble-burying behavior may involve preoccupation with objects, it is possible that simultaneous measurements of burying and locomotion may yield inappropriate results, since animals engaging in burying activity may travel shorter overall distances than animals engaging in normal exploratory routines (de Brouwer & Wolmarans, 2018).…”

Section: Locomotor Performancementioning

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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“…It is well established that a plausible cause of OCD is abnormal cortical-striatal-thalamic circuitry activation (Ahmari et al, 2013) and altered serotonergic (Schilman et al, 2010), glutamatergic (Arnold et al, 2004; Egashira et al, 2013; Porton et al, 2013) and GABAergic (Egashira et al, 2013) systems. Interestingly, female hormones, such as estrogen and P4, regulate various neurotransmitter signaling pathways in brain regions implicated in OCD (Dreher et al, 2007; Karakaya et al, 2007; Benmansour et al, 2009; Alonso et al, 2011; Quinlan et al, 2013; Barth et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Ovarian Sex Hormones Modulate Compulsive, Affective and Cognitive Functions in A Non-Induced Mouse Model of Obsessive-Compulsive Disorder

Mitra

Bastos

Bates

et al. 2016

Front. Behav. Neurosci.

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There is currently a lack of understanding of how surgical menopause can influence obsessions, compulsions and associated affective and cognitive functions in female obsessive-compulsive disorder (OCD) patients. Early menopause in women due to surgical removal of ovaries not only causes dramatic hormonal changes, but also may induce affective and cognitive disorders. Here, we tested if surgical removal of ovaries (ovariectomy, OVX), which mimics surgical menopause in humans, would result in exacerbation of compulsive, affective and cognitive behaviors in mice strains that exhibit a spontaneous compulsive-like phenotype. Female mice from compulsive-like BIG, non-compulsive SMALL and randomly-bred Control strains were subjected to OVX or sham-surgery. After 7 days animals were tested for nest building and marble burying to measure compulsive-like behavior. The elevated plus maze and open field tests measured anxiety-like behaviors, while memory was assessed by the novel object recognition. Acute OVX resulted in exacerbation of compulsive-like and anxiety-like behaviors in compulsive-like BIG mice. No significant effects of OVX were observed for the non-compulsive SMALL and Control strains. Object recognition memory was impaired in compulsive-like BIG female mice compared to the Control mice, without an effect of OVX on the BIG mice. We also tested whether 17 β-estradiol (E2) or progesterone (P4) could reverse the effects of OVX. E2, but not P4, attenuated the compulsive-like behaviors in compulsive-like BIG OVX female mice. The actions of the sex steroids on anxiety-like behaviors in OVX females were strain and behavioral test dependent. Altogether, our results indicate that already existing compulsions can be worsened during acute ovarian deprivation concomitant with exacerbation of affective behaviors and responses to hormonal intervention in OVX female mice can be influenced by genetic background.

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Effects of mood stabilizers on marble-burying behavior in mice

Abstract: These results suggest that GABAergic mechanism is involved in marble-burying behavior, and that valproate, carbamazepine and lamotrigine reduce marble-burying behavior. Moreover, valproate reduces marble-burying behavior via a GABA(A) receptor-dependent mechanism.

Cited by 18 publications

References 67 publications

Behavioral Characteristics of Ubiquitin-Specific Peptidase 46-Deficient Mice

Behavioral Characteristics of Ubiquitin-Specific Peptidase 46-Deficient Mice

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

Ovarian Sex Hormones Modulate Compulsive, Affective and Cognitive Functions in A Non-Induced Mouse Model of Obsessive-Compulsive Disorder

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