Reduced impact of emotion on choice behavior in presymptomatic BACHD rats, a transgenic rodent model for Huntington Disease

Adjeroud, Najia; Yagüe, S.; Yu-Taeger, Libo; Bozon, Bruno; Leblanc-Veyrac, Pascale; Rieß, Olaf; Allain, Philippe; Nguyen, Huu Phuc; Doyère, Valérie; Massioui, Nicole El

doi:10.1016/j.nlm.2015.10.003

Cited by 11 publications

(15 citation statements)

References 44 publications

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“…In the RGT, adapted from Rivalan et al (2009) and as described in Adjeroud et al (2015), rats have to face four options reinforced by an immediate reward. They have to learn that two options are associated with a greater reward, but are disadvantageous in the long run due to higher penalties.…”

Section: Methodsmentioning

confidence: 99%

“…This dysexecutive syndrome is often associated with other behavioral consequences such as disinhibition (often concomitantly with apathy) and impulsivity/compulsivity (Duff et al, 2007; Beglinger et al, 2008; Reedeker et al, 2011). Few studies have directly examined symptoms and consequences of behavioral disinhibition in HD (Busemeyer and Stout, 2002; Stout et al, 2011; Holl et al, 2013) and only two studies have assessed risky decision-making abilities (Adjeroud et al, 2015) and levels of impulsivity in a transgenic rat model of HD (Manfré et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

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Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

Massioui

Lamirault

Yagüe

et al. 2016

Front. Behav. Neurosci.

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Cognitive deficits associated with Huntington disease (HD) are generally dominated by executive function disorders often associated with disinhibition and impulsivity/compulsivity. Few studies have directly examined symptoms and consequences of behavioral disinhibition in HD and its relation with decision-making. To assess the different forms of impulsivity in a transgenic model of HD (tgHD rats), two tasks assessing cognitive/choice impulsivity were used: risky decision-making with a rat gambling task (RGT) and intertemporal choices with a delay discounting task (DD). To assess waiting or action impulsivity the differential reinforcement of low rate of responding task (DRL) was used. In parallel, the volume as well as cellular activity of the amygdala was analyzed. In contrast to WT rats, 15 months old tgHD rats exhibited a poor efficiency in the RGT task with difficulties to choose advantageous options, a steep DD curve as delays increased in the DD task and a high rate of premature and bursts responses in the DRL task. tgHD rats also demonstrated a concomitant and correlated presence of both action and cognitive/choice impulsivity in contrast to wild type (WT) animals. Moreover, a reduced volume associated with an increased basal cellular activity of the central nucleus of amygdala indicated a dysfunctional amygdala in tgHD rats, which could underlie inhibitory dyscontrol. In conclusion, tgHD rats are a good model for impulsivity disorder that could be used more widely to identify potential pharmacotherapies to treat these invasive symptoms in HD.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

Massioui

Lamirault

Yagüe

et al. 2016

Front. Behav. Neurosci.

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“…It should, however, be noted that in most of these studies the initial training steps were performed when the rats were 2–5 months old, and learning deficits might still be present in older animals. In line with this, it has been found that 18 months old BACHD rats (but not 2 and 8 months old rats) required more sessions than WT rats to reach criterion when learning to perform single nose pokes for food rewards [33]. However, no detailed analysis was performed to investigate if this phenotype was based on the rats having actual difficulties to associate the instrumental response with the delivery of a food pellet, or rather them being less interested in exploring the test chamber.…”

Section: Discussionmentioning

confidence: 83%

The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory

Clemensson

Rieß

et al. 2017

PLoS ONE

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The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

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“…The battery of tests lasted about 2 months. All animals were naïve for all these tests even though groups 1 and 3 previously performed a rat gambling task in another study …”

Section: Methodsmentioning

confidence: 99%

“…In symptomatic animals at 12 months of age, emotional blunting associated with an hypersensitivity to negative emotional situations also appeared, evidencing a dysfunctional emotional regulation. In another rat model, at 4 months, BACHD rats showed a reduced anxiety in the elevated plus maze and a reduced impact of emotion on executive functions from 2 months of age . In conclusion, studies of emotional regulation remains sparse and have contradictory results, with some of them showing hyper‐anxiety, as in patients, whereas most of the others suggesting a phenotype of hypo‐anxiety, opposite results that may reflect age‐related modulations the time‐course of which may depend on the animal model used.…”

Section: Introductionmentioning

confidence: 91%

Age‐related alteration of emotional regulation in the BACHD rat model of Huntington disease

Lamirault

Nguyen

Doyère

et al. 2020

Genes Brain and Behavior

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Huntington's disease (HD) is a genetic neurodegenerative disorder, caused by an expanded CAG repeat in the gene encoding the huntingtin protein. At the premanifest phase, before motor symptoms occur, psychiatric and emotional disorders are observed with high prevalence in HD patients. Agitation, anxiety and irritability are often described but also depression and/or apathy, associated with a lack of emotional control. The aim of the present study was to better circumscribe and understand the emotional symptoms and assess their evolution according to the progression of the disease using a transgenic HD model, BACHD rats, at the age of 4, 12 and 18 months. To achieve this goal, we confronted animals to two types of tests: first, tests assessing anxiety like the light/dark box and the conflict test, which are situations that did not involve an obvious threat and tests assessing the reactivity to a present threat using confrontation with an unknown conspecific (social behavior test) or with an aversive stimulus (fear conditioning test). In all animals, results show an age-dependent anxiety-like behavior, particularly marked in situation requiring passive responses (light/dark box and fear conditioning tests). BACHD rats exhibited a more profound alteration than WT animals in these tests from an early stage of the disease whereas, in tasks requiring some kind of motivation (for food or for social contacts), only old BACHD rats showed high anxiety-like behavior compared to WT, may be partly due to the other symptoms' occurrence at this stage: locomotor difficulties and/or apathy. K E Y W O R D Sage-related deficits, anxiety, behavioral assessement, behavioral inhibition, fear conditioning, emotional regulation, Huntington disease, rat, reactivity to threat, social behavior

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Reduced impact of emotion on choice behavior in presymptomatic BACHD rats, a transgenic rodent model for Huntington Disease

Cited by 11 publications

References 44 publications

Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory

Age‐related alteration of emotional regulation in the BACHD rat model of Huntington disease

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