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C05 Differential-reinforcement-of-low-rates-of-responding-task Performance In A Transgenic Rat Model Of Huntington Disease
  1. G Manfré1,
  2. H Phuc Nguyen1,
  3. V Doyère2,3,
  4. N El Massioui2,3
  1. 1Department of Medical Genetics, University of Tuebingen, 72076 Tuebingen, Germany
  2. 2Université Paris-Sud, Centre de Neurosciences Paris-Sud, Unité Mixte de Recherche 8195, F-91405 Orsay, France
  3. 3Centre National de La Recherche Scientifique, F-91405 Orsay, France


Psychiatric changes, dementia and motor dysfunction are hallmarks of Huntington disease (HD), a neurodegenerative disorder genetically characterised by the presence of expanded CAG repeats in the HTT gene.The behavioural characterisation of a valid rodent model for HD is critical, especially in light of the development of therapeutic strategies for HD. BACHD transgenic rats, carrying the human full length mutated HTT (97 CAG-CAA repeats) display a robust, early onset and progressive HD-like phenotype including motor deficits and anxiety-related symptoms. We evaluated the impulsive action (IA), defined as the inability to withhold a prepotent motor response.IA of 5 months old BACHD rats was assessed using the DRL (Differential Reinforcement of Low rates of responding task). Rats were trained progressively through a series of two reinforcement schedules (DRL-5 and -10 s) that required them to withhold responding for the appropriate amount of time before a lever press was reinforced. Relative to controls, BACHD rats displayed a decrease in response efficiency during DRL-10. This lack was not present during the DRL-5 schedule, showing that BACHD rats can withhold an instrumental response only for short periods of time. We also observed that BACHD rats displayed deficits in behavioural inhibition (i.e. increased responding during non-reinforced periods) that were mainly evident during the ‘burst’ (0–2s inter response time, IRT) in the DRL-10 schedule.Taken together, these data suggest that deficits in the ability to inhibit lever press responding at increasing IRTs predict greater impulsive action of this transgenic rat model of Huntington’s disease.

  • Huntington disease
  • Impulsivity
  • Behaviour

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