Excessive nest building is a unique behavioural phenotype in the deer mouse model of obsessive–compulsive disorder

Abstract

Obsessive-compulsive disorder (OCD) is a phenotypically heterogeneous condition characterised by time-consuming intrusive thoughts and/or compulsions. Irrespective of the symptom type diagnosed, the severity of OCD is characterised by heterogeneity in symptom presentation that complicates diagnosis and treatment. Heterogeneity of symptoms would be invaluable in an animal model. Nest building behaviour forms part of the normal behavioural repertoire of rodents and demonstrates profound between-species differences. However, it has been proposed that within-species differences in nest building behaviour (i.e. aberrant vs. normal nest building) may resemble obsessive-compulsive-like symptoms. In an attempt to investigate whether other obsessive-compulsive-like behaviours are present in an animal model of OCD, or if aberrant nest building behaviour may represent a unique obsessive-compulsive phenotype in such a model, the current study assessed nest building behaviour in high (H, viz obsessive-compulsive) and non (N, viz normal) stereotypical deer mice. Subsequently, 12 N and H animals, respectively, were provided with an excess of cotton wool daily for one week prior to and following four weeks of high-dose oral escitalopram treatment (50 mg/kg/day). Data from the current investigation demonstrate daily nesting activity to be highly variable in deer mice, with stereotypy and nest building being independent behaviours. However, we identified unique aberrant large nest building behaviour in 30% of animals from both cohorts that was attenuated by escitalopram to pre-treatment nesting scores of the larger group. In summary, behavioural and drug-treatment evidence confirms that deer mouse behaviour does indeed resemble symptom heterogeneity related to OCD, and as such expands its face and predictive validity for the disorder.

Obsessive-compulsive disorder: Insights from animal models

“…Environmental enrichment partially suppresses the expression of stereotypy, also prompting delayed presentation (Hadley et al, 2006; Powell et al, 1999), indicating that confinement stress is more a triggering factor than an etiological determinant, and since compulsions can be distinguished from rigid motor patterns on the basis of thoughtfulness (Eilam et al, 2006), deer mouse stereotypy can be regarded as flexible. Also deer mouse stereotypy appears to be associated with social deficits, is independent of anxiety and presents with symptom heterogeneity with regard to other forms of compulsive-like behavior that has value for studying the obsessive-compulsive interface of OCD (Section 4.3; Wolmarans et al, 2016a,b,c). As in OCD (Evans et al, 2004; Husted et al, 2006; Markarian et al, 2010) and as emphasized in the earlier two models (Sections 2 and 3), high stereotypic (H) deer mice also present with frontal cortical pathology, e.g., disordered redox balance (Guldenpfennig et al, 2011) and altered cyclic adenosine-monophosphate (cAMP)-phosphodiesterase (PDE) signaling (Korff et al, 2009).…”

“…NB behavior in deer mice is highly variable, with no evident differences as a function of severity of stereotypy (Wolmarans et al, 2016c). However, as described for marble burying behavior above, a sub-population from both H and N cohorts present with large NB behavior.…”

Natural compulsive‐like behaviour in the deer mouse (Peromyscus maniculatus bairdii) is associated with altered gut microbiota composition

“…Regarded collectively, natural compulsive-like behavioural phenotypes expressed by deer mice (Peromyscus maniculatus bairdii), that is large nest building (LNB) and high stereotypy, provide a well-validated naturalistic pre-clinical framework in which to study the etiopathology of OCD (Scheepers, Scheepers, Stein, & Harvey, 2018). Approximately 30% of laboratory housed deer mice of both sexes express LNB (Wolmarans, Stein, & Harvey, 2016). LNB manifests by the age of 8 weeks and is persistent and repetitive over the course of several trials.…”

Attenuation of Compulsive-Like Behavior Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Non-Induced Compulsive-Like Mice

“…The Control mice therefore serve as a selection control with intermediate levels between compulsive-like BIG and non-compulsive SMALL strains (Bult and Lynch, 2000). NB is homologous to hoarding in humans with OCD (Warneke, 1993), which is considered to be a measure of compulsive-like phenotype in mice (Greene-Schloesser et al, 2011; Wolmarans De et al, 2016). The BIG mice also uniformly display repetitive marble burying (MB) behavior burying on an average 19–20 marbles.…”