Androgen receptor activation is involved in maintaining goal-directed behavior in levonorgestrel-treated female rats

Levonorgestrel (LNG), a contraceptive hormone, is used by millions of women worldwide. We have found that LNG delays habit expression in gonadally-intact female rats, suggesting it influences cognitive processes. The mechanism driving LNG's effect on habit in female rats remains unclear. One explanation is that LNG's androgenic properties impact habit learning. To investigate this, intact female rats were implanted subcutaneously with either cholesterol- (Experiment 1) or LNG- (Experiment 2) capsules. Animals from each group received subcutaneous injections of flutamide, an androgen receptor antagonist, or vehicle prior to sessions of appetitive operant training. After training, half of the rats in each experimental group received outcome devaluation, which rendered the sucrose reward aversive. Subsequently, all rats underwent a short extinction test to ascertain whether behavior was goal-directed or habitual. In Experiment 1, habit was observed in cholesterol-implanted females, and this was not affected by flutamide, replicating our earlier finding that habit is present after moderate training in intact female rats, and additionally showing that blocking androgen receptor activity during training does not alter habit expression. In Experiment 2, LNG-implanted rats exhibited goal-directed behavior, again replicating our previous findings showing that LNG delays habit in female rats. However, LNG-implanted rats treated with flutamide during training displayed habitual behavior, suggesting that the androgenic effects of LNG are responsible, at least in part, for delaying habit expression in intact female rats. This finding suggests that the androgenic properties of LNG are exerting significant effects on cognitive processes related to behavioral flexibility in the female brain.