Browsing by Subject "Trichotillomania"

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    Predictive Value of Grooming Behavior for Development of Dermatitis in Selectively Bred P Rats as a Model of Trichotillomania Hair Pulling Disorder
    (MDPI, 2022-02-18) Hickman, Debra; Prakash, Anjali; Bell, Richard; Psychiatry, School of Medicine
    Trichotillomania (TTM) is a body-focused repetitive disorder affecting as much as 0.5 to 2% of the population, with women four times more likely to be affected than men. This disorder causes impairment in daily function and significant distress. A potential animal model for this disorder is the inbred C57BL/6J mouse which displays clinical signs and behavioral characteristics similar to those described for people affected by this disorder. Because alcohol-preferring P rats also display similar clinical signs and behavioral characteristics, it was hypothesized that this selectively bred stock could be an additional animal model. In this study, 112 female P rats were recorded on digital media for 15 min after being sprayed with a mist of water and assessed for grooming patterns—oral, manual, and scratching. Significant elevations in scratching and oral grooming behavior were predictive of the future development of skin lesions. These findings suggest that P rats may be an additional model to study TTM, with the advantage of increased genetic variation (i.e., non-inbred) which mirrors the human population. The use of this model may help to identify preventative and therapeutic interventions for humans and other animals with similar body-focused repetitive disorders.
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    Spinophilin Limits Metabotropic Glutamate Receptor 5 Scaffolding to the Postsynaptic Density and Cell Type Specifically Mediates Excessive Grooming
    (Elsevier, 2023) Morris, Cameron W.; Watkins, Darryl S.; Shah, Nikhil R.; Pennington, Taylor; Hens, Basant; Qi, Guihong; Doud, Emma H.; Mosley, Amber L.; Atwood, Brady K.; Baucum, Anthony J., II; Pharmacology and Toxicology, School of Medicine
    Background: Grooming dysfunction is a hallmark of the obsessive-compulsive spectrum disorder trichotillomania. Numerous preclinical studies have utilized SAPAP3-deficient mice for understanding the neurobiology of repetitive grooming, suggesting that excessive grooming is caused by increased metabotropic glutamate receptor 5 (mGluR5) activity in striatal direct- and indirect-pathway medium spiny neurons (MSNs). However, the MSN subtype-specific signaling mechanisms that mediate mGluR5-dependent adaptations underlying excessive grooming are not fully understood. Here, we investigated the MSN subtype-specific roles of the striatal signaling hub protein spinophilin in mediating repetitive motor dysfunction associated with mGluR5 function. Methods: Quantitative proteomics and immunoblotting were utilized to identify how spinophilin impacts mGluR5 phosphorylation and protein interaction changes. Plasticity and repetitive motor dysfunction associated with mGluR5 action were measured using our novel conditional spinophilin mouse model in which spinophilin was knocked out from striatal direct-pathway MSNs and/or indirect-pathway MSNs. Results: Loss of spinophilin only in indirect-pathway MSNs decreased performance of a novel motor repertoire, but loss of spinophilin in either MSN subtype abrogated striatal plasticity associated with mGluR5 function and prevented excessive grooming caused by SAPAP3 knockout mice or treatment with the mGluR5-specific positive allosteric modulator VU0360172 without impacting locomotion-relevant behavior. Biochemically, we determined that the spinophilin-mGluR5 interaction correlates with grooming behavior and that loss of spinophilin shifts mGluR5 interactions from lipid raft-associated proteins toward postsynaptic density proteins implicated in psychiatric disorders. Conclusions: These results identify spinophilin as a novel striatal signaling hub molecule in MSNs that cell subtype specifically mediates behavioral, functional, and molecular adaptations associated with repetitive motor dysfunction in psychiatric disorders.