Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease.
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.
Institut des Neurosciences Paris-Saclay (Neuro-PSI), UMR 9197, Centre National de la Recherche Scientifique (CNRS) Université Paris Sud, Université Paris Saclay Orsay, France.
Nicole
N
El Massioui
Institut des Neurosciences Paris-Saclay (Neuro-PSI), UMR 9197, Centre National de la Recherche Scientifique (CNRS) Université Paris Sud, Université Paris Saclay Orsay, France.
Charlotte
C
Lamirault
Institut des Neurosciences Paris-Saclay (Neuro-PSI), UMR 9197, Centre National de la Recherche Scientifique (CNRS) Université Paris Sud, Université Paris Saclay Orsay, France.
Sara
S
Yagüe
Institut des Neurosciences Paris-Saclay (Neuro-PSI), UMR 9197, Centre National de la Recherche Scientifique (CNRS) Université Paris Sud, Université Paris SaclayOrsay, France; Neuropsychological Unit, Department of Neurology, CHU AngersFrance.
Najia
N
Adjeroud
The Graduate Center, City University of New York (CUNY) New York, NY, USA.
Daniel
D
Garces
Institut des Neurosciences Paris-Saclay (Neuro-PSI), UMR 9197, Centre National de la Recherche Scientifique (CNRS) Université Paris Sud, Université Paris Saclay Orsay, France.
Alexis
A
Maillard
Institut des Neurosciences Paris-Saclay (Neuro-PSI), UMR 9197, Centre National de la Recherche Scientifique (CNRS) Université Paris Sud, Université Paris Saclay Orsay, France.
Lucille
L
Tallot
Institute of Medical Genetics and Applied Genomics, University of TuebingenTuebingen, Germany; Center for Rare Diseases, University of TuebingenTuebingen, Germany.
Libo
L
Yu-Taeger
Institute of Medical Genetics and Applied Genomics, University of TuebingenTuebingen, Germany; Center for Rare Diseases, University of TuebingenTuebingen, Germany.
Olaf
O
Riess
Neuropsychological Unit, Department of Neurology, CHU Angers France.
Philippe
P
Allain
Institute of Medical Genetics and Applied Genomics, University of TuebingenTuebingen, Germany; Center for Rare Diseases, University of TuebingenTuebingen, Germany.
Huu Phuc
HP
Nguyen
Experimental Therapy, Franz Penzoldt Center, Friedrich-Alexander University, Erlangen-Nürnberg Germany.
Stephan
S
von Hörsten
Institut des Neurosciences Paris-Saclay (Neuro-PSI), UMR 9197, Centre National de la Recherche Scientifique (CNRS) Université Paris Sud, Université Paris Saclay Orsay, France.
Valérie
V
Doyère
DRL; Huntington disease; decision-making; delay discounting; gambling task; impulsivity