Background Cognitive deterioration mainly characterised as frontal-executive deficits is intrinsic to Huntington’s disease (HD) and identifiable years before motor-based clinical onset. Although behavioural, cognitive and neuropathological changes have been described in a novel BACHD rat model, little is known about the presence of measurable frontal-executive alterations in pre-symptomatic animals.
Objectives We aimed to investigate set-shifting performance in a longitudinal approach along the course of the disease. Here we present the cross-sectional results.
Methods Wild type (n = 20) and transgenic (n = 20) male BACHD rats were tested at 8 weeks-aged. Motor function (locomotor activity) was assessed through a photoelectric actimeter.Set-shifting performance was evaluated through the attentional set-shifting paradigm described by Birrell and Brown. Reversal learning and acquisition/shifting on intra-dimensional (IDS) and extra-dimensional (EDS) stages were measured. The total number of trials done to achieve six consecutive correct responses was used as performance measure. Data were subjected to unpaired t-test and repeated measures ANOVA.
Results No alterations in clasping behaviour were found in BACHD rats. Compared to wild-type, BACHD rats appeared significantly slower (964.8 ± 58.6 vs 1300 ± 73.6; p = 0.002). No differences were found regarding reversal learning and IDS. Conversely, BACHD rats made a significantly higher number of EDS errors than wild-type (14.6 ± 0.6 vs 12 ± 0.4; p < 0.001).
Conclusions A well differentiated pattern of more impaired set-shifting performance is measurable in transgenic animals and distinguishes BACHD from wild-type rats during the pre-symptomatic stage. Despite longitudinal data are needed, set-shifting performance apparels as a potentially useful biomarker to track the progression of the disease in the BACHD rat model.
- Huntington’s disease