Oestrogen treatment modulates the impact of cognitive experience and task complexity on memory in middle-aged surgically menopausal rats

Menopause has been linked to changes in memory. Oestrogen-containing hormone therapy is prescribed to treat menopause-related symptoms and can ameliorate memory changes, although the parameters impacting oestrogen-related memory efficacy are unclear. Cognitive experience and practice have been shown to be neuroprotective and to improve learning and memory during ageing, with the type of task playing a role in subsequent cognitive outcomes. Whether task complexity matters, and whether these outcomes interact with menopause and oestrogen status, remains unknown. To investigate this, we used a rat model of surgical menopause to systematically assess whether maze task complexity, as well as order of task presentation, impacts spatial learning and memory during middle age when rats received vehicle, low-17β-oestradiol (E₂) or high-E₂ treatment. The direction, and even presence, of the effects of prior maze experience differed depending on the E₂ dose. Surgical menopause without E₂ treatment yielded the least benefit, as prior maze experience did not have a substantial effect on subsequent task performance for vehicle treated rats regardless of task demand level during the first exposure to maze experience or final testing. High-dose E₂ yielded a variable benefit, and low-dose E₂ produced the greatest benefit. Specifically, low-dose E₂ broadly enhanced learning and memory in surgically menopausal rats that had prior experience on another task, regardless of the complexity level of this prior experience. These results demonstrate that E₂ dose influences the impact of prior cognitive experience on learning and memory during ageing, and highlights the importance of prior cognitive experience in subsequent learning and memory outcomes.