Escitalopram and lorazepam differentially affect nesting and open field behaviour in deer mice exposed to an anxiogenic environment

Wolmarans, De Wet; Prinsloo, Michelle; Seedat, Soraya; Stein, Dan J.; Harvey, Brian H.; Brouwer, Geoffrey de

doi:10.1016/j.neures.2021.10.011

Cited by 7 publications

(11 citation statements)

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“…To explain, considering that both NS and HS animals present with stereotypical behaviors, albeit to different degrees, and that LOR administered on its own elicited stereotypical expression in NS animals during the remainder of the dark-cycle post-R, it is possible that differences in anxiety-processing biology in NS and HS animals could have differentially modulated the effects of LOR in this model system. We have previously shown that LOR elicits a behavioral response in this species (albeit in compulsive-like large-nesting subjects under conditions of open-field stress), that was proposed to be reminiscent of behavioral disinhibition (Wolmarans et al, 2022). Here, we propose that under conditions of acute stress, i.e., R, such a response is seen in animals of the HS phenotype, while a similar response to LOR is only seen in NS animals in the absence of an acute stressor (Figure 4); conversely, under the latter conditions, LOR has no effect on the behavioral output of HS animals.…”

Section: Discussionmentioning

confidence: 99%

“…Earlier work investigating behavioral disinhibition in drug- (Constantinou et al, 2010 ) and alcohol users (Zack et al, 2011 ) elegantly showed that high states of emotional arousal, as is true for anxiogenic circumstances, can either blunt or increase behavioral disinhibition. If we consider then that NS and HS animals may present with unique anxiety-like behavioral profiles (Wolmarans et al, 2022 ), it is possible that differences in the anxiogenic valence of R-related feedback in NS and HS mice could have uniquely influenced the manner in which LOR elicited the observed responses. Benzodiazepines are known to cause behavioral disinhibition in a context-sensitive manner (Paton, 2002 ), a phenomenon that has been shown in both pre-clinical (Ferrari et al, 1997 ) and clinical (Weisman et al, 1998 ) settings.…”

Section: Discussionmentioning

confidence: 99%

“…Escitalopram oxalate [ESC; BLD Pharma ® , Shanghai, China; 50 mg/kg/day; Wolmarans et al ( 2013 )] and LOR [Aspen Pharmacare ® , Qheberha, South Africa; 2 mg/kg/day; Wolmarans et al ( 2022 )] were prepared for sub-acute (8-day) and chronic (35-day) oral administration via the drinking water, respectively. These concentrations were based on the average daily liquid consumption of deer mice [0.25 ml/g/day; Wolmarans et al ( 2013 ) and de Brouwer et al ( 2020 )].…”

Section: Methodsmentioning

confidence: 99%

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Behavioral restriction, lorazepam, and escitalopram uniquely influence the expression of naturalistic stereotypy in deer mice: perspectives on anxiety- and compulsive-like behavior

Burke

Mograbi

Wolmarans

2022

Front. Behav. Neurosci.

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Introduction: Stereotypical expression in laboratory-housed rodents can be explained by different motivational, coping, and motor dysfunction theories. Here, we aimed to explore the neurocognitive underpinnings of high stereotypical (HS) expression in deer mice (Peromyscus maniculatus bairdii), previously proposed as a model system of compulsive-like behavioral persistence. Specifically, we aimed to establish whether HS behavior is related to an underlying escape-related trigger.Methods: One-hundred and sixteen deer mice were classified as either non-stereotypical (NS) or HS. Mice of each cohort were further subdivided and exposed to either sub-acute (3-day) or chronic (25-day) behavioral restriction (R), and high-dose escitalopram (ESC), lorazepam (LOR), alone and in combination with R (ESC+R and LOR+R, respectively). Mice were reassessed for stereotypical behavior at both time points.Results: Our results indicate that HS behavior is likely not temporally and functionally related to an anxiogenic trigger, i.e., R, but rather that HS is associated with parallel changes in anxiogenic feedback processing. We also show that chronic R alone significantly decreased the time spent in expressing HS behavior in animals of the HS, but not NS phenotype.Discussion: This points to the possibility that HS-expressing mice represent a subgroup of P. maniculatus bairdii in which unique interactions between neurobiology and processes of gradual behavioral organization, may contribute to the expression of the typical behaviors observed in this cohort. Collectively, our findings highlight the value of the deer mouse model system to investigate the potential neurocognitive mechanisms that may underlie the development of persistent phenotypes that can likely not be explained entirely by current theories.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Behavioral restriction, lorazepam, and escitalopram uniquely influence the expression of naturalistic stereotypy in deer mice: perspectives on anxiety- and compulsive-like behavior

Burke

Mograbi

Wolmarans

2022

Front. Behav. Neurosci.

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“…10,386:2021). The number of animals included in this investigation was broadly based on extensive prior investigation where we showed that at least 30-45% of mice develop LNB [34,[36][37][38][39] and motor stereotypies [40][41][42][43] in adulthood.…”

Section: Study Layoutmentioning

confidence: 99%

Associations between nesting, stereotypy, and working memory in deer mice: response to levetiracetam

2023

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Background Some deer mice (Peromyscus maniculatus bairdii) exhibit various phenotypes of persistent behaviors. It remains unknown if and how said phenotypes associate with early-life and adult cognitive perturbations, and whether potentially cognitive enhancing drugs might modify such associations. Here, we explored the longitudinal relationship between early-life behavioral flexibility and the expression of persistent behavior in adulthood. We also investigated how said phenotypes might associate with working memory in adulthood, and how this association might respond to chronic exposure to the putative cognitive enhancer, levetiracetam (LEV). Methods 76 juvenile deer mice were assessed for habit-proneness in the Barnes maze (BM) and divided into two exposure groups (n = 37–39 per group), i.e., control and LEV (75 mg/kg/day). After 56 days of uninterrupted exposure, mice were screened for nesting and stereotypical behavior, and then assessed for working memory in the T-maze. Results Juvenile deer mice overwhelmingly utilize habit-like response strategies, regardless of LNB and HS behavior in adulthood. Further, LNB and HS are unrelated in terms of their expression, while LEV reduces the expression of LNB, but bolsters CR (but not VA). Last, an increased level of control over high stereotypical expression may facilitate improved working memory performance. Conclusion LNB, VA and CR, are divergent in terms of their neurocognitive underpinnings. Chronic LEV administration throughout the entire rearing period may be of benefit to some phenotypes, e.g., LNB, but not others (CR). We also show that an increased level of control over the expression of stereotypy may facilitate improved working memory performance.

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“…While a detailed review of biobehavioral differences between NNB and LNB mice falls beyond the scope of the present work (see Wolmarans et al. (2022), Saaiman et al. (2023), Wolmarans et al.…”

Section: Introductionmentioning

confidence: 99%

Large nesting expression in deer mice remains stable under conditions of visual deprivation despite heightened limbic involvement: Perspectives on compulsive‐like behavior

Marx,

Krahe,

Wolmarans

2024

J of Neuroscience Research

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Visual stimuli and limbic activation varyingly influence obsessive‐compulsive symptom expression and so impact treatment outcomes. Some symptom phenotypes, for example, covert repugnant thoughts, are likely less sensitive to sensory stimuli compared to symptoms with an extrinsic focus, that is, symptoms related to contamination, safety, and “just‐right‐perceptions.” Toward an improved understanding of the neurocognitive underpinnings of obsessive‐compulsive psychobiology, work in naturalistic animal model systems is useful. Here, we explored the impact of visual feedback and limbic processes on 24 normal (NNB) and large (LNB) nesting deer mice, respectively (as far as possible, equally distributed between sexes). Briefly, after behavioral classification into either the NNB or LNB cohorts, mice of each cohort were separated into two groups each and assessed for nesting expression under either standard light conditions or conditions of complete visual deprivation (VD). Nesting outcomes were assessed in terms of size and neatness. After nesting assessment completion, mice were euthanized, and samples of frontal‐cortical and hippocampal tissues were collected to determine serotonin and noradrenaline concentrations. Our results show that LNB, as opposed to NNB, represents an inflexible and excessive behavioral phenotype that is not dependent on visually guided action‐outcome processing, and that it associates with increased frontal‐cortical and hippocampal noradrenaline concentrations, irrespective of lighting condition. Collectively, the current results are informing of the neurocognitive underpinnings of nesting behavior. It also provides a valuable foundation for continued investigations into the noradrenergic mechanisms that may influence the development and promulgation of excessive, rigid, and inflexible behaviors.

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Escitalopram and lorazepam differentially affect nesting and open field behaviour in deer mice exposed to an anxiogenic environment

Cited by 7 publications

References 47 publications

Behavioral restriction, lorazepam, and escitalopram uniquely influence the expression of naturalistic stereotypy in deer mice: perspectives on anxiety- and compulsive-like behavior

Behavioral restriction, lorazepam, and escitalopram uniquely influence the expression of naturalistic stereotypy in deer mice: perspectives on anxiety- and compulsive-like behavior

Associations between nesting, stereotypy, and working memory in deer mice: response to levetiracetam

Large nesting expression in deer mice remains stable under conditions of visual deprivation despite heightened limbic involvement: Perspectives on compulsive‐like behavior

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