Effects of hormonal contraceptives on spatial navigation in gonadally intact female rats

Rats can either use place memory, response memory or rely on a single cue to navigate their environment. Which navigation strategy a female rat is biased towards is influenced by circulating levels of ovarian hormones. Hormonal contraceptive use is typically associated with changes in circulating levels of endogenous ovarian hormones. The aim of the current study was to examine the effects of synthetic hormones used in hormonal contraceptives on navigation strategies. A total of 61 gonadally intact female rats were tested in two Morris water maze tasks. Rats were administered ethinyl estradiol (EE; 10 μg/kg; n = 10), levonorgestrel (LNG; 20 μg/kg, n = 10), a combination of both EE and LNG (10 μg/kg and 20 μg/kg, n = 10), or vehicle control (n = 31). Controls were tested during either proestrus (n = 10), estrus (n = 11) or diestrus (n = 10). In the place vs. response task, proestrus females exhibited an initial place memory bias while estrus females exhibited an initial response memory bias (OR = 18). However, all groups, apart from the EE + LNG group, eventually spent more time in the place quadrant (η² = 0.53), suggesting a corrective shift towards place memory when unable to locate the platform. In the cue task, all groups, apart from the EE + LNG, showed an initial bias to the other quadrant (η² = 0.41). This initial bias was abolished in all groups, apart from proestrus females, by the end of the probe. The EE + LNG group failed to exhibit a bias for any of the navigation strategies throughout, suggesting that this formulation of combined EE + LNG may impede memory bias formation.