Q03 Effects of tetrabenazine on choreiform movements in the transgenic rat model of Huntington's disease

Background Open-label studies indicate that tetrabenazine (TBZ), a reversible inhibitor of the vesicular monoamine transporter type 2, is effective in reducing the chorea in patients with Huntington9s disease (HD). Animal models of HD are used to understand the pathophysiology of the disease and to find new therapies. In this respect, few years ago the first transgenic rat model of HD (tgHD) has been introduced. These animals show hyperkinetic movements, which have not been well characterised. Aims We assessed and characterised the hyperkinetic movements in detail and investigated the effect of TBZ therapy. Methods We evaluated the hyperkinetic movements of a group (n=11) of 17 months old homozygous male tgHD rats. The animals were videotaped in their home cage environment before and after receiving a subcutaneous injection with TBZ (2.5 mg/kg) or vehicle. Each animal received both conditions. The evaluation was done every 15 min, before and after the animal received an injection, during a 5 min assessment period. The observer was blinded with respect to the condition of the rats. Results The tgHD rats showed abrupt, rapid, brief and un-sustained irregular movement of the neck. None of these movements were observed in other parts of the body. We found that administration of TBZ reduced the number of these hyperkinetic movements on average with 55% (p Conclusion The hyperkinetic movement disorder observed in the tgHD rats can be considered as a choreiform movement, based on the characteristic of the movement and the positive response to TBZ administration.