Short-term memory acquisition in female Huntington's disease mice is vulnerable to acute stress

•Short-term memory deficit (assessed in the Y-maze) appears earlier in R6/1 HD males.•Acute stress induced memory impairment only in HD female animals.•However, stress-induced corticosterone release was not exaggerated in female HD mice.

Huntington's disease (HD) is a neurodegenerative disorder marked by cognitive, psychiatric and motor decline, and is modifiable by unidentified environmental factors. We examined the effects of stress on cognitive function in R6/1 HD transgenic mice. Utilizing the Y-maze to assess short-term memory, we report that only female HD mice displayed vulnerability to 1 h of confinement stress reflected by impaired memory acquisition. This could not be attributed to a different corticosterone response or exploratory behaviour in the task. This is the first demonstration of increased stress susceptibility in an animal model of HD involving a direct negative impact on cognitive function.