Predictive validity of a non-induced mouse model of compulsive-like behavior

Abstract

A key to advancing the understanding of obsessive-compulsive disorder (OCD)-like symptoms is the development of spontaneous animal models. Over 55 generations of bidirectional selection for nest-building behavior in house mice, Mus musculus, resulted in a 40-fold difference in the amount of cotton used for a nest in high (BIG) and low (SMALL) selected lines. The nesting behavior of BIG mice appears to be compulsive-like and has initial face validity as an animal model for OCD in humans. Compulsive-like digging behavior was assessed; BIG male mice buried about three times as many marbles as SMALL male mice, strengthening face validity. Using the open field and elevated plus maze, SMALL male mice showed higher levels of anxiety/fear-like behavior than BIG male mice, indicating that compulsive-like and not anxiety-like behavior was measured. To establish predictive validity, chronic (4 weeks) oral administration of fluoxetine (30, 50 and 100 mg/kg/day) and clomipramine (80 mg/kg/day), both effective in treating OCD, significantly reduced compulsive-like nest-building behavior in BIG male mice. Compulsive-like digging behavior was also significantly reduced by chronic oral fluoxetine (30 and 80 mg/kg/day) treatment in BIG male mice. General locomotor activity was not affected by chronic oral fluoxetine (30 and 80 mg/kg/day) treatment; chronic oral treatment with desipramine (30 mg/kg/day), an antidepressant not effective in treating OCD, had no effect on nesting behavior of BIG male mice, strengthening predictive validity. Together, the results indicate that these mice have good face and predictive validity as a non-induced mouse model of compulsive-like behavior relevant to OCD.

Melanin concentrating hormone modulates oxytocin-mediated marble burying

“…To test whether OT infusion reduces repetitive behavior in mice, we investigated its effect in marble burying task (Deacon, 2006; Thomas et al, 2009; Greene-Schloesser et al, 2011; Angoa-Perez et al, 2013). We found that i.c.v.…”

“…It has been suggested as a screening test for anxiolytic response, but more recently has been proposed as modeling repetitive behaviors characteristic of mental disorders such as obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD) (Thomas et al, 2009; Greene-Schloesser et al, 2011; Angoa-Perez et al, 2013; Aguilar-Valles et al, 2015; Mitra et al, 2016a, 2016b, 2017). …”

Marble burying as compulsive behaviors in male and female mice

“…MB has features not observed in other anxiety paradigms. For example, burying will occur in the safety of the home cage, in the absence of obvious fear or stressful stimuli and burying fails to habituate over test sessions (Chotiwat and Harris 2006, Greene-Schloesser et al 2011, Thomas et al 2009). …”

Activation of the orbitofrontal and anterior cingulate cortices during the expression of a naturalistic compulsive-like behavior in the rabbit

“…We propose that a detailed understanding of this "stop mechanism" should shed light on neural processes that are altered in OCD [32]. In support of this proposal, recent studies indicate that processes that control nonmaternal nest building in mice might be related to those underlying obsessive-compulsive symptoms [26,64].…”