Altered emotional and motivational processing in the transgenic rat model for Huntington's disease.
Huntington disease (HD) is caused by an expansion of CAG repeat in the Huntingtin gene. Patients demonstrate a triad of motor, cognitive and psychiatric symptoms. A transgenic rat model (tgHD rats) carrying 51 CAG repeats demonstrate progressive striatal degeneration and polyglutamine aggregates in limbic structures. In this model, emotional function has only been investigated through anxiety studies. Our aim was to extend knowledge on emotional and motivational function in symptomatic tgHD rats. We subjected tgHD and wild-type rats to behavioral protocols testing motor, emotional, and motivational abilities. From 11 to 15 months of age, animals were tested in emotional perception of sucrose using taste reactivity, acquisition, extinction, and re-acquisition of discriminative Pavlovian fear conditioning as well as reactivity to changes in reinforcement values in a runway Pavlovian approach task. Motor tests detected the symptomatic status of tgHD animals from 11 months of age. In comparison to wild types, transgenic animals exhibited emotional blunting of hedonic perception for intermediate sucrose concentration. Moreover, we found emotional alterations with better learning and re-acquisition of discriminative fear conditioning due to a higher level of conditioned fear to aversive stimuli, and hyper-reactivity to a negative hedonic shift in reinforcement value interpreted in term of greater frustration. Neuropathological assessment in the same animals showed a selective shrinkage of the central nucleus of the amygdala. Our results showing emotional blunting and hypersensitivity to negative emotional situations in symptomatic tgHD animals extend the face validity of this model regarding neuropsychiatric symptoms as seen in manifest HD patients, and suggest that some of these symptoms may be related to amygdala dysfunction.
Univ Paris-Sud, Centre de Neurosciences Paris-Sud, UMR 8195, Orsay F-91405, France. alexis.faure@u-psud.fr
A
A
Faure
S
S
Höhn
S
S
Von Hörsten
B
B
Delatour
K
K
Raber
P
P
Le Blanc
N
N
Desvignes
V
V
Doyère
N
N
El Massioui
D000679:Amygdala / Q000473:pathology / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology*; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004644:Emotions / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009042:Motivation / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology; D009048:Motor Skills / Q000502:physiology; D009714:Nucleus Accumbens / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D055647:Rats, Transgenic