B010 Behavioural changes and opisthotonus-like movements in the F344tgHD transgenic rat model of Huntington’s disease

<h3>Background</h3> A range of genetic mouse models are available to study Huntington’s disease (HD), although most have CAG repeats well in excess of that seen in adult HD and a relatively aggressive disease progression. The transgenic F344tgHD rat expresses a 51 CAG repeat fragment and exhibits a slow progressive phenotype that may be more typical of human adult-onset HD. <h3>Aims</h3> We sought to characterise motor and cognitive changes in the F344tgHD transgenic rat model, with a focus on understanding the manifestation of opisthotonus-like movements. <h3>Methods</h3> Wild type (WT), low mHTT expressing (mHTT low) and high mHTT expressing (mHTT high) rats were assessed for motor and cognitive deficits. Opisthotonos-like movements were quantified longitudinally, with pharmacological modulation at 5 and 18 months of age. The 5-choice serial reaction time task (5CSRTT), probing cognitive function, was undertaken at 12 months of age. <h3>Results</h3> Opisthotonos-like movements were observed in mHTT high rats as early as 2 months of age and persisted throughout the animal’s lifetime. Pharmacological challenge indicated these to be dopamine-mediated-behaviours. In the 5CSRTT, mHTT high rats performed significantly fewer total trials, were significantly less impulsive and omitted more responses compared to WT rats. <h3>Conclusion</h3> These data suggest that alterations of the dopamine system may be instrumental in the manifestation of opisthotonos-like movements in the F344tgHD rats. F344tgHD rats also demonstrate motivational deficits. This data will contribute to a larger longitudinal analysis of F344tgHD rat behaviour that aims to provide a more slowly progressive HD model for therapeutic testing, combined with the advantages of the larger rat brain.