A behavioural exploration of litter effect in normal and compulsive-like large nesting behaviour

Abstract

Obsessive compulsive disorder (OCD)1 is a debilitating neuropsychiatric disorder which is diagnosed if the obsessions, compulsions, or both, meet specific diagnostic criteria. The disorder is characteristically different from general anxiety disorder, although anxiety is regularly present in OCD. Although selective serotonin reuptake inhibitors (SSRIs)2 are currently considered to be the mainstay of its treatment, more than 40 % of patients remain non-responsive. The disorder is thus conceptualised as a condition of hyposerotonergic signalling. While its exact aetiology and pathophysiology are not yet fully understood genetic heritability is proposed to play a role. What remains entirely unclear, is if and to what extent genetic factors contribute to perturbations in one or more of the neurocognitive domains associated with OCD. Therefore, it remains difficult to advance our current understanding of the condition since the impact of specific gene-biology-behaviour interactions in the disorder, is not yet elucidated. Since longitudinal studies in clinical cohorts are difficult considering the lifespan of humans, research in preclinical models, like the present, is vital. When housed under standard laboratory conditions, approximately 30 % of deer mice (Peromyscus maniculatus bairdii) spontaneously express excessive, compulsive-like large nesting behaviour (LNB)3. LNB is regarded as an excessive goal-directed behavioural routine. LNB can be born from genetic or other biological factors or processes related to experiential learning, especially since the evolutionary and naturalistic purpose of nesting is to ensure breeding and nursing success. With respect to LNB in deer mice, it is still unclear if LNB, as opposed to normal nesting behaviour (NNB)4, may represent a superior form of goal-directed behaviour that serves to improve breeding outcomes or whether we are correct to conclude that such behaviour is compulsive-like, and thus devoid of an actual, realistic function. It is further unknown if LNB is related to familial factors, which may point to a genetic construct underlying its presentation. The focus of the present investigation was to answer this question. To fully address the aims and objectives of this work, fifty-seven deer mice from both sexes (28 female; 29 male) were bred and reared from eleven randomly selected breeding pairs at the vivarium of the 1 obsessive compulsive disorder 2 selective serotonin reuptake inhibitors 3 large nest building 4 normal nest building North-West University (NWU)1, Potchefstroom, South Africa. All mice underwent nesting screening at the age of 12 - 20 weeks. From these, 14 LNB2 expressing mice and 14 NNB3 expressing mice (equally distributed between sexes) were selected and paired, considering that littermates were not paired together. These seven NNB and LNB breeding pairs were left to breed two generations of offspring (for Chapter 3) and a third in LNB breeding pairs (to add to the adult offspring screened in Chapter 4 of this work). Nesting expression was then assessed in all adult offspring of the seven NNB and LNB breeding pairs, and the data represented in Chapter 4. The first main finding showed that despite being as fertile as NNB mice, offspring born from most LNB expressing pairs are notably less viable. Considering that nesting serves several evolutionary conserved functions, this finding was striking in showing that naturalistic LNB in deer mice is goalless and likely born from dysfunctional psychobiological processes. Such a conclusion was supported by our second main finding, which showed that offspring from LNB expressing pairs built significantly larger nests than offspring from NNB pairs and that offspring from specific breeding pairs built similar sized nests, irrespective of the litter they came from. Since mice could not have expressed the present behaviour as an outcome of experiential learning, we can conclude with a relative degree of confidence that NNB and LNB are two distinct behavioural phenotypes founded upon heritable mechanisms. While the deer mouse model is a valuable model system in which to explore the psychobiological triggers that give rise to spontaneous compulsive-like behavioural persistence, future investigations should explore the nature of the familial influences shown here.