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Altered emotional and motivational processing in the transgenic rat model for Huntington's disease
A Faure1, S Höhn, S Von Hörsten
1Univ Paris-Sud, Centre de Neurosciences Paris-Sud, UMR 8195, Orsay F-91405, France. alexis.faure@u-psud.fr
Insights
Huntington disease (HD) rat models show emotional blunting and hypersensitivity to negative stimuli, suggesting amygdala dysfunction contributes to neuropsychiatric symptoms in HD patients.
Area of Science:
- Neuroscience
- Genetics
- Behavioral Science
Background:
- Huntington disease (HD) stems from CAG repeat expansion in the Huntingtin gene, causing motor, cognitive, and psychiatric symptoms.
- Transgenic HD (tgHD) rats with 51 CAG repeats model striatal degeneration and polyglutamine aggregates, but emotional function remains understudied.
- Existing research on tgHD rats has primarily focused on anxiety, limiting understanding of broader emotional and motivational deficits.
Purpose of the Study:
- To investigate emotional and motivational function in symptomatic tgHD rats.
- To extend the face validity of the tgHD rat model for Huntington disease neuropsychiatric symptoms.
- To explore the relationship between observed behavioral alterations and neuropathology, specifically amygdala function.
Main Methods:
- tgHD and wild-type rats were assessed using behavioral tests for motor, emotional, and motivational capacities between 11 and 15 months of age.
- Tests included sucrose taste reactivity, Pavlovian fear conditioning (acquisition, extinction, re-acquisition), and a runway task assessing reactivity to reinforcement value changes.
- Neuropathological analysis focused on the amygdala in the same cohort of animals.
Main Results:
- Symptomatic tgHD rats exhibited emotional blunting in hedonic perception of intermediate sucrose concentrations.
- tgHD rats demonstrated enhanced learning and re-acquisition of fear conditioning, indicating higher conditioned fear to aversive stimuli.
- These animals showed hyper-reactivity to negative shifts in reinforcement value, interpreted as increased frustration, alongside selective shrinkage of the central amygdala nucleus.
Conclusions:
- Symptomatic tgHD rats display emotional blunting and hypersensitivity to negative emotional situations, mirroring neuropsychiatric symptoms in human Huntington disease patients.
- These findings enhance the face validity of the tgHD rat model for studying HD-related emotional and motivational deficits.
- Dysfunction within the amygdala, particularly the central nucleus, may underlie some of the observed emotional alterations in Huntington disease.
Abstract:
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.
