Correction: Further investigation of phenotypes and confounding factors of progressive ratio performance and feeding behavior in the BACHD rat model of Huntington disease

Clemensson, Erik Karl Håkan; Clemensson, Laura Emily; Fabry, Benedikt; Flunkert, Stefanie; Rieß, Olaf; Wronski, Robert; Nguyen, Huu Phuc

doi:10.1371/journal.pone.0213755

Cited by 2 publications

(1 citation statement)

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“…The impaired PR performance exhibited by the R6/1 mice, ahead of any motor deficits, further increases the face and construct validity of these animals as a means to explore HD motivational deficits (60). Impairments in motivation to earn reward have been reported in other HD rodent models including the BAC HD, z_Q175 KI and Hdh mouse strains (61–65) and the BACHD rat (66–68). Given that the R6/1 mouse is widely studied, particularly with respect to novel therapeutics, it offers a powerful platform, in combination with the PR task, to deliver novel insights into the pathophysiological mechanisms underlying this early onset HD symptom and to evaluate potential therapeutic avenues.…”

Section: Discussionmentioning

confidence: 88%

A Touchscreen Motivation Assessment Evaluated in Huntington's Disease Patients and R6/1 Model Mice

et al. 2019

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Apathy is pervasive across many neuropsychiatric disorders but is poorly characterized mechanistically, so targeted therapeutic interventions remain elusive. A key impediment has been the lack of validated assessment tools to facilitate translation of promising findings between preclinical disease models and patients. Apathy is a common symptom in Huntington's disease. Due to its established genetic basis and the availability of defined animal models, this disease offers a robust translational framework for linking motivated behavior with underlying neurobiology and an ideal context in which to evaluate a quantitative, translational apathy assessment method. In this study we therefore aimed to demonstrate the validity of using touchscreen-delivered progressive ratio tasks to mirror apathy assessment in Huntington's disease patients and a representative mouse model. To do this we evaluated Huntington's disease patients ( n = 23) and age-matched healthy controls ( n = 20), and male R6/1 mice ( n = 23) and wildtype controls ( n = 29) for apathy-like behavior using touchscreen-delivered progressive ratio tasks. The primary outcome measure of the assessment was breakpoint, defined as the highest number of touchscreen responses emitted before task engagement ceased. Patients and R6/1 mice were both found to exhibit significantly reduced breakpoints relative to their respective control groups, consistent with apathy-like behavior. This performance was also not associated with motoric differences in either species. These data demonstrate the utility of touchscreen-delivered progressive ratio tasks in detecting clinically relevant motivational deficits in Huntington's disease. This approach may offer a platform from which clinically relevant mechanistic insights concerning motivation symptoms can be derived and provide an effective route for translation of promising preclinical findings into viable therapeutic interventions.

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