Article

The mouse who couldn't stop washing: pathologic grooming in animals and humans.

UCLA Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
CNS spectrums (Impact Factor: 1.3). 09/2009; 14(9):503-13.
Source: PubMed

ABSTRACT The basic science literature is replete with descriptions of naturally occurring or experimentally induced pathological grooming behaviors in animals, which are widely considered animal models of obsessive-compulsive disorder (OCD). These animal models rely largely on observed similarities between animal behaviors and human OCD behaviors, and on studies of animal pathological grooming disorders that respond to serotonin enhancing drugs. However, current limitations in assessment of complex cognition and affect in animals precludes the field's ability to match the driving primary processes behind observable phenomenology in animal "OCD" with human behavioral disorders. We propose that excessive grooming behaviors in animals may eventually prove to be equally, or possibly more relevant to, other conditions in humans that involve pathological grooming or grooming-like behaviors, such as trichotillomania, body dysmorphic disorder, olfactory reference syndrome, compulsive skin-picking, and onychophagia. Research is needed to better understand pathological grooming behaviors in both humans and animals, as animal models have the potential to elucidate pathogenic mechanisms and inform the treatment of these psychiatric conditions in humans.

Download full-text

Full-text

Available from: Jamie Feusner, Mar 28, 2014
0 Followers
 · 
107 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rodent self-grooming is an important, evolutionarily conserved behavior, highly sensitive to pharmacological and genetic manipulations. Mice with aberrant grooming phenotypes are currently used to model various human disorders. Therefore, it is critical to understand the biology of grooming behavior, and to assess its translational validity to humans. The present in-silico study used publicly available gene expression and behavioral data obtained from several inbred mouse strains in the open-field, light-dark box, elevated plus- and elevated zero-maze tests. As grooming duration differed between strains, our analysis revealed several candidate genes with significant correlations between gene expression in the brain and grooming duration. The Allen Brain Atlas, STRING, GoMiner and Mouse Genome Informatics databases were used to functionally map and analyze these candidate mouse genes against their human orthologs, assessing the strain ranking of their expression and the regional distribution of expression in the mouse brain. This allowed us to identify an interconnected network of candidate genes (which have expression levels that correlate with grooming behavior), display altered patterns of expression in key brain areas related to grooming, and underlie important functions in the brain. Collectively, our results demonstrate the utility of large-scale, high-throughput data-mining and in-silico modeling for linking genomic and behavioral data, as well as their potential to identify novel neural targets for complex neurobehavioral phenotypes, including grooming.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 10/2012; 40. DOI:10.1016/j.pnpbp.2012.10.015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Obsessive-compulsive disorder (OCD) is a common and often debilitating neuropsychiatric condition characterized by persistent intrusive thoughts (obsessions), repetitive ritualistic behaviors (compulsions) and excessive anxiety. While the neurobiology and etiology of OCD has not been fully elucidated, there is growing evidence that disrupted neurotransmission of glutamate within corticalstriatal-thalamocortical (CSTC) circuitry plays a role in OCD pathogenesis. This review summarizes the findings from neuroimaging, animal model, candidate gene and treatment studies in the context of glutamate signaling dysfunction in OCD. First, studies using magnetic resonance spectroscopy are reviewed demonstrating altered glutamate concentrations in the caudate and anterior cingulate cortex of patients with OCD. Second, knockout mouse models, particularly the DLGAP3 and Sltrk5 knockout mouse models, display remarkably similar phenotypes of compulsive grooming behavior associated with glutamate signaling dysfunction. Third, candidate gene studies have identified associations between variants in glutamate system genes and OCD, particularly for SLC1A1 which has been shown to be associated with OCD in five independent studies. This converging evidence for a role of glutamate in OCD has led to the development of novel treatment strategies involving glutamatergic compounds, particularly riluzole and memantine. We conclude the review by outlining a glutamate hypothesis for OCD, which we hope will inform further research into etiology and treatment for this severe neuropsychiatric condition.
    Pharmacology Biochemistry and Behavior 02/2012; 100(4):726-35. DOI:10.1016/j.pbb.2011.10.007
  • Source
    [Show abstract] [Hide abstract]
    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 100mg/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.
    Behavioural brain research 02/2011; 221(1):55-62. DOI:10.1016/j.bbr.2011.02.010