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Cereb Cortex. 2019 Feb 7. doi: 10.1093/cercor/bhz009. [Epub ahead of print]

Motivational Impairment is Accompanied by Corticoaccumbal Dysfunction in the BACHD-Tg5 Rat Model of Huntington's Disease.

Author information

1
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn St., Baltimore, MD, USA.
2
Department of Stereotaxy and Functional Neurosurgery, University Hospital of Cologne, Kerpener Str. 62 Cologne, Germany.
3
CHDI Foundation, 6080 Center Drive, Suite 700, Los Angeles, CA, USA.
4
Department of Psychiatry, University of Maryland School of Medicine, 20 Penn St., Baltimore, MD, USA.

Abstract

Neuropsychiatric symptoms, such as avolition, apathy, and anhedonia, precede the onset of debilitating motor symptoms in Huntington's disease (HD), and their development may give insight into early disease progression and treatment. However, the neuronal and circuit mechanisms of premanifest HD pathophysiology are not well-understood. Here, using a transgenic rat model expressing the full-length human mutant HD gene, we find early and profound deficits in reward motivation in the absence of gross motor abnormalities. These deficits are accompanied by significant and progressive dysfunction in corticostriatal processing and communication among brain areas critical for reward-driven behavior. Together, our results define early corticostriatal dysfunction as a possible pathogenic contributor to psychiatric disturbances and may help identify potential pharmacotherapeutic targets for the treatment of HD.

PMID:
30753343
DOI:
10.1093/cercor/bhz009

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