Estrogen effects on the forced swim test differ in two outbred rat strains

Changes in reproductive hormones, such as estrogen, play a role in mood regulation. The present study examined strain differences (Long-Evans vs. Wistar-Hannover) in the behavioral and biochemical effects of estrogen manipulation. Adult ovariectomized female rats were treated with estradiol, vehicle, or withdrawn from estradiol. The two strains demonstrated differential behavioral responses to short-term estradiol administration in the forced swim test; estradiol induced an antidepressant-like effect in Long-Evans rats but not in Wistar rats. Conversely, withdrawal from estradiol resulted in a depressive-like state in the Wistar rats but not in the Long-Evans rats. Western blot analyses found no differences in estrogen receptors α and β within the hippocampus or the frontal cortex, two brain areas strongly implicated in affective disorders. These data demonstrate the importance of strain as a variable when interpreting behavioral effects of estrogen.

► Data suggest strain-dependent differential behavioral sensitivity to estradiol. ► Estradiol produced an anti-depressant behavior in Long-Evans rats but not in Wistar rats. ► Estradiol withdrawal induced depressant-like behavior in Wistar rats but not in Long-Evans rats. ► No differences in estradiol levels, ER alpha or ER beta protein levels were found between the strains.