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

• Published in: Behavioural brain research 2020-09, Vol.393, p.112794-112794, Article 112794
• Main Authors: de Brouwer, Geoffrey, Fick, Arina, Lombaard, Ané, Stein, Dan J., Harvey, Brian H., Wolmarans, De Wet
• Format: Article
• Language: English
• Subjects: Deer mouse model; Escitalopram; Marble-burying test; Nest building; OCRDs
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2020.112794

•Large nest building (LNB) and high marble burying (HMB) are two naturalistic, but unique compulsive-like and persistent behavioural phenotypes expressed by deer mice.•LNB is reminiscent of a SSRI-sensitive phenotype, responding to the SSRI, escitalopram and a combination of escitalopram and the dopaminergic antagonist, flupentixol.•HMB represents a SSRI-resistant phenotype, but shows response to pro-dopaminergic intervention, i.e. the monoaminoxidase type B inhibitor, rasagiline.•LNB and HMB can potentially be applied to elucidate the unique contributions of serotonin and dopamine to different, but equally persistent, behavioural phenotypes that are reminiscent of different obsessive-compulsive or related disorders. This study aimed to further dissect the deer mouse (Peromyscus maniculatus bairdii) model of compulsive-like behavior with respect to two persistent-like behavioral phenotypes viz. large nest building (LNB) and high marble-burying (HMB), which may be relevant to understanding the neurobiology of different symptom dimensions in obsessive-compulsive and related disorders. Since LNB is sensitive to chronic, high dose escitalopram intervention but HMB is not, we assessed whether the two behaviors could be further distinguished based on their response to 4 weeks of uninterrupted serotoninergic intervention (i.e. escitalopram; ESC; 50 mg/kg/day), dopaminergic antagonism, i.e. flupentixol; FLU; 0.9 mg/kg/day), dopaminergic potentiation (i.e. rasagiline; RAS; 5 mg/kg/day), and their respective combinations with escitalopram (ESC/FLU and ESC/RAS). Here we show LNB to be equally responsive to chronic ESC and ESC/FLU. HMB was insensitive to either of these interventions but was responsive to ESC/RAS. Additionally, we report that scoring preoccupied interaction with marbles over several trials is an appropriate measure of compulsive-like behavioral persistence in addition to the standard marble burying test. Taken together, these data provide further evidence that LNB and HMB in deer mice have distinctive neurobiological underpinnings. Thus, the naturally occurring compulsive-like behaviors expressed by deer mice may be useful in providing a platform to test unique treatment targets for different symptom dimensions of OCD and related disorders.