Differential effects of chronic 17β-oestradiol treatment on rat behaviours relevant to depression

Sex differences are a prominent feature of the pathophysiology of psychiatric disorders, such as major depressive disorder, which affects women at a higher incidence than men. Research suggests that the most potent endogenous oestrogen, 17β-oestradiol, may have therapeutic potential in treating depression. However, preclinical studies have produced mixed results, likely as a result of various methodological factors such as treatment duration. The present study aimed to investigate the effects of ovariectomy and chronic 17β-oestradiol treatment via a s.c. silastic implant on behaviours relevant to depression in adult female Sprague-Dawley rats. Rats were assessed in the forced swim test, saccharin preference test and novel object recognition memory test, as well as for possible confounding behaviours, including locomotion and anxiety (open field test) and motivation and anxiety (novelty suppressed feeding test). Treatment effects were verified using body and uterus weight, as well as serum concentrations of 17β-oestradiol, progesterone and testosterone. Compared to ovariectomised rats, chronic 17β-oestradiol treatment enhanced saccharin preference and novel object recognition performance. There were no group differences in passive or active coping behaviour when assayed using the forced swim test. Taken together, these results support an antidepressant-like action of oestrogens but highlight that the beneficial effects of chronic 17β-oestradiol treatment may be related to specific depression-related symptoms, particularly anhedonia and memory.