Reappraisal of spontaneous stereotypy in the deer mouse as an animal model of obsessive-compulsive disorder (OCD): Response to escitalopram treatment and basal serotonin transporter (SERT) density

Wolmarans, De Wet; Brand, Linda; Stein, Dan J.; Harvey, Brian H.

doi:10.1016/j.bbr.2013.08.049

Cited by 43 publications

(91 citation statements)

References 48 publications

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“…In order to screen animals for baseline expression of stereotypy, the same protocol as published previously (Wolmarans et al, 2013) was followed. In short, all animals underwent a 12-h behavioral screening once a week for five consecutive screens.…”

Section: Generating Behavioral Data and The Classification Of N And Hmentioning

confidence: 99%

“…Following the first five behavioral screens, the animals were divided into N and H groups according to our previously published protocol (Wolmarans et al, 2013). Because the findings from previous studies had demonstrated the timeconsuming nature of stereotypy, we amended the protocol to include both the intensity (number of stereotypical counts per 30 min) and frequency (number of 30-min H bouts per 12-h dark cycle or time spent executing stereotypy) as indicators of behavioral severity.…”

Section: Generating Behavioral Data and The Classification Of N And Hmentioning

confidence: 99%

“…The rationale for the exclusion of a gray margin of animals is to improve sensitivity, as we have described elsewhere (Wolmarans et al, 2013).…”

Section: Generating Behavioral Data and The Classification Of N And Hmentioning

confidence: 99%

“…As opposed to learned or pharmacologically induced perseverative behavior, spontaneous stereotypy in the deer mouse (Peromyscus maniculatus bairdii) is a naturalistic animal model of OCD, founded on robust face, construct, and predictive validity (Güldenpfennig, Wolmarans, du Preez, Stein, & Harvey, 2011;Korff, Stein, & Harvey, 2008Wolmarans, Brand, Stein, & Harvey, 2013). Deer mouse stereotypy can generally be categorized into repetitive jumping and pattern running (Korff et al, 2008;Powell, Newman, Pendergast, & Lewis, 1999), behaviors that correspond with the repetitive motor actions of OCD.…”

mentioning

confidence: 99%

“…Deer mouse stereotypy can generally be categorized into repetitive jumping and pattern running (Korff et al, 2008;Powell, Newman, Pendergast, & Lewis, 1999), behaviors that correspond with the repetitive motor actions of OCD. Furthermore, deer mouse stereotypy demonstrates varying symptom intensities, as in OCD, and "time spent executing stereotypy" is employed as a marker of behavioral severity and treatment outcome (Wolmarans et al, 2013). Although deer mouse stereotypy has not yet been studied with respect to anxiety-like behavior, it demonstrates response to chronic, but not to subchronic, treatment with high doses of a selective serotonin reuptake inhibitor (SSRI) that is similarly effective in the treatment of anxiety and compulsive behavior in humans (Wolmarans et al, 2013).…”

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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: Generating Behavioral Data and The Classification Of N And Hmentioning

confidence: 99%

Section: Generating Behavioral Data and The Classification Of N And Hmentioning

confidence: 99%

“…The rationale for the exclusion of a gray margin of animals is to improve sensitivity, as we have described elsewhere (Wolmarans et al, 2013).…”

Section: Generating Behavioral Data and The Classification Of N And Hmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

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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Adult Offspring of Deer Mouse Breeding Pairs Selected for Normal and Compulsive‐Like Large Nesting Expression Invariably Show the Same Behavior Without Prior In‐Breeding

Stoppel,

Harvey,

Wolmarans

2024

Developmental Psychobiology

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Obsessive‐compulsive disorder is a neuropsychiatric condition with notable genetic involvement. Against this background, laboratory‐housed deer mice of both sexes varyingly present with excessive and persistent large nesting behavior (LNB), which has been validated for its resemblance of clinical compulsivity. Although LNB differs from normal nesting behavior (NNB) on both a biological and cognitive level, it is unknown to what extent the expression of LNB and NNB is related to familial background. Here, we randomly selected 14 NNB‐ and 14 LNB‐expressing mice (equally distributed between sexes) to constitute 7 breeding pairs of each phenotype. Pairs were allowed to breed two successive generations of offspring, which were raised until adulthood (12 weeks) and assessed for nesting expression. Remarkably, our findings show that offspring from LNB‐expressing pairs build significantly larger nests compared to offspring from NNB‐expressing pairs and the nesting expression of the offspring of each breeding pair, irrespective of parental phenotype or litter, is family specific. Collectively, the results of this investigation indicate that LNB can be explored for its potential to shed light on heritable neurocognitive mechanisms that may underlie the expression of specific persistent behavioral phenotypes.

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Stereotypy and spontaneous alternation in deer mice and its response to anti‐adenosinergic intervention

Browuer

Engelbrecht

Mograbi

et al. 2021

J of Neuroscience Research

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Repetitive behavioral phenotypes are a trait of several neuropsychiatric disorders, including obsessive-compulsive disorder (OCD). Such behaviors are typified by complex interactions between cognitive and neurobiological processes which most likely contribute to the suboptimal treatment responses often observed. To this end, exploration of the adenosinergic system may be useful, since adenosine-receptor modulation has previously shown promise to restore control over voluntary behavior and improve cognition in patients presenting with motor repetition. Here, we employed the deer mouse (Peromyscus maniculatus bairdii) model of compulsive-like behavioral persistence, seeking to investigate possible associations between stereotypic motor behavior and cognitive flexibility as measured in the T-maze continuous alternation task (T-CAT). The effect of istradefylline, a selective adenosine A 2A receptor antagonist at two doses (10 and 20 mg kg −1 day −1 ) on the expression of stereotypy and T-CAT performance in high (H) and non-(N) stereotypical animals, was investigated in comparison to a control intervention (six groups; n = 8 or 9 per group). No correlation between H behavior and T-CAT performance was found. However, H but not N animals presented with istradefylline-sensitive spontaneous alternation and stereotypy, in that istradefylline at both doses significantly improved the spontaneous alternation scores and attenuated the stereotypical expression of H animals. Thus, evidence is presented that anti-adenosinergic drug action improves repetitive behavior and spontaneous alternation in stereotypical deer mice, putatively pointing to a shared psychobiological construct underlying naturalistic stereotypy and alterations in cognitive flexibility in deer mice.

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Reappraisal of spontaneous stereotypy in the deer mouse as an animal model of obsessive-compulsive disorder (OCD): Response to escitalopram treatment and basal serotonin transporter (SERT) density

Cited by 43 publications

References 48 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

Adult Offspring of Deer Mouse Breeding Pairs Selected for Normal and Compulsive‐Like Large Nesting Expression Invariably Show the Same Behavior Without Prior In‐Breeding

Stereotypy and spontaneous alternation in deer mice and its response to anti‐adenosinergic intervention

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