Large nest building and high marble-burying: Two compulsive-like phenotypes expressed by deer mice (Peromyscus maniculatus bairdii) and their unique response to serotoninergic and dopamine modulating intervention

Brouwer, Geoffrey de; Fick, Arina; Lombaard, Ane; Stein, Dan J.; Harvey, Brian H.; Wolmarans, De Wet

doi:10.1016/j.bbr.2020.112794

Cited by 9 publications

(16 citation statements)

References 80 publications

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“…That said, from Figures 3–6, it is evident that, as it stands, the behavior of both sexes is represented across the reported ranges. This finding is broadly in line with our previous research (de Brouwer, Fick, et al., 2020; Wolmarans et al., 2013), but would need substantial future investigation to confirm. Still, given that the animals included in this investigation were clustered based on behavioral expression, that is without considering sex as a potential biological variable, the chosen group sizes were determined to be adequate for comparisons of stereotypical expression.…”

Section: Discussionsupporting

confidence: 92%

“…The same solution was administered without the addition of drug to control‐exposed animals. Importantly, deer mice drink fluid at an average rate of 0.25 ml/g/24 hr (de Brouwer, Fick, et al., 2020). Although this has not been shown to change as a function of drug exposure or additives added to the drinking water (de Brouwer, Fick, et al., 2020; de Brouwer, Harvey, et al., 2020), the average daily fluid intake per cage was monitored by weighing the residual amount of liquid left on each following day (Supplementary Information).…”

Section: Methodsmentioning

confidence: 99%

“…Importantly, deer mice drink fluid at an average rate of 0.25 ml/g/24 hr (de Brouwer, Fick, et al., 2020). Although this has not been shown to change as a function of drug exposure or additives added to the drinking water (de Brouwer, Fick, et al., 2020; de Brouwer, Harvey, et al., 2020), the average daily fluid intake per cage was monitored by weighing the residual amount of liquid left on each following day (Supplementary Information). Istradefylline was constituted in concentrations that ensured the delivery of the appropriate doses to animals over a 24‐hr period (4 and 8 mg/100 ml for the 10 and 20 mg kg −1 day −1 doses, respectively).…”

Section: Methodsmentioning

confidence: 99%

“…For example, Shen et al (2008) found that extrastriatal A 2A receptor (eA 2A ) blockade (and knockout) attenuated the ambulatory and rearing responses of mice dosed with the dopamine transporter inhibitor, cocaine; in contrast, such behavior was aggravated by the specific blocking or knocking out of striatal A 2A receptors (sA 2A ). Moreover, eA 2A , but not sA 2A blockade has been shown to maintain synaptic plasticity (Costenla et al, 2011).…”

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confidence: 99%

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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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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…Additionally, nests were weighed at time 0 and 6 hours, and the amount of nestlet used was calculated by subtracting the intact portion of the nestlet remaining at 6 hours from the original nestlet weight at time 0. Reductions in nest building are thought to reflect reduced well-being (53,54). For all measures, outliers were removed if their value was greater than two standard deviations above or below the mean.…”

Section: Dig Testmentioning

confidence: 99%

Mice lackingPtprdexhibit deficits in goal-directed behavior and female-specific impairments in sensorimotor gating

Welch

et al. 2022

Preprint

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Protein Tyrosine Phosphatase receptor type D (PTPRD) is a member of the protein tyrosine phosphatase family that mediates cell adhesion and synaptic specification. Genetic studies have linked Ptprd to several neuropsychiatric phenotypes, including Restless Leg Syndrome (RLS), opioid abuse disorder, and antipsychotic-induced weight gain. Genome-wide association studies (GWAS) of either pediatric obsessive-compulsive traits, or Obsessive-Compulsive Disorder (OCD), have identified loci near Ptprd as genome-wide significant, or strongly suggestive for this trait. We assessed Ptprd wild-type (WT), heterozygous (HT), and knockout (KO) mice for behavioral dimensions that are altered in OCD, including anxiety and exploration (open field test, dig test), perseverative behavior (splash-induced grooming, spatial d), sensorimotor gating (prepulse inhibition), and home cage goal-directed behavior (nest building). No effect of genotype was observed in any measure of the open field test, dig test, or splash test. However, Ptprd KO mice of both sexes showed impairments in nest building behavior. Finally, female, but not male, Ptprd KO mice showed deficits in prepulse inhibition, an operational measure of sensorimotor gating that is reduced in female, but not male, OCD patients. Our results indicate that constitutive lack of Ptprd may contribute to the development of certain domains that are altered OCD, including goal-directed behavior, and reduced sensorimotor gating specifically in females.

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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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Large nest building and high marble-burying: Two compulsive-like phenotypes expressed by deer mice (Peromyscus maniculatus bairdii) and their unique response to serotoninergic and dopamine modulating intervention

Cited by 9 publications

References 80 publications

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

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

Mice lackingPtprdexhibit deficits in goal-directed behavior and female-specific impairments in sensorimotor gating

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

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