Early Cognitive Dysfunction in the HD 51 CAG Transgenic Rat Model of Huntington's Disease

Mark P Reilly, Kyle David Fink, Gary Dunbar, K. K. Davis, Michael I Sandstrom, Julien Pierre Andre Rossignol, Steven Allen Lowrance, Andrew Crane, Angela M. Bavar, Nicholas W. Dekorver, Stephan von Hörsten, Laurent Lescaudron

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Huntington's disease (HD) is a neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat that produces choreic movements, which are preceded by cognitive deficits. The HD transgenic rat (tgHD), which contains the human HD mutation with a 51 CAG repeat allele, exhibits motor deficits that begin when these rats are 12 months of age. However, there are no reports of cognitive dysfunction occurring prior to this. To assess whether cognitive dysfunction might precede motor deficits in tgHD rats, one group of 9-month-old male rats with homozygotic mutated genes and one group of wild-type (WT) rats underwent three testing phases in a unique Spatial Operant Reversal Test (SORT) paradigm, as well as assessment of spontaneous motor activity. After testing, morphological and histological examination of the brains were made. Results indicated that tgHD rats acquired the cued-response (Phase 1) portion of the SORT, but made significantly more errors during the reversal (Phase 2) and during the pseudorandomized reversals (Phase 3) portion of the study, when compared to WT rats. Analysis of the data using mathematical principles of reinforcement revealed no memory, motor, or motivational deficits. These results indicate that early cognitive dysfunction, as measured by the SORT, occur prior to motor deficits, gross anatomical changes, or cell loss in the tgHD rat with 51 CAG repeats, and suggest that this protocol could provide a useful screen for therapeutic studies.

Original languageEnglish
Pages (from-to)479-487
Number of pages9
JournalBehavioral Neuroscience
Issue number3
StatePublished - Jun 2012


  • Cognitive dysfunction
  • HD 51 CAG
  • Huntington's disease
  • Neurodegenerative disorder
  • Operant conditioning
  • Transgenic rat


Dive into the research topics of 'Early Cognitive Dysfunction in the HD 51 CAG Transgenic Rat Model of Huntington's Disease'. Together they form a unique fingerprint.

Cite this