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Hormonal contraceptives (HCs), particularly those containing ethinyl estradiol (EE) and levonorgestrel (LNG), are widely used, yet their effects on adolescent brain and behaviour remain underexplored. Here, we investigated the effects of EE and LNG on anxiety-like and social behaviours in adolescent and adult female rats, and whether social instability stress (SS) exacerbates these effects. We predicted that adolescents may be more susceptible to the effects of HCs and SS than adults, given ongoing brain development in adolescence. Sixty-four adolescent (postnatal day (PND) 22) and 64 adult (PND62) gonadally-intact female Long-Evans rats were randomized to SS or control groups, and then to HC (10 μg/kg EE, 20 μg/kg LNG) or vehicle treatment daily for 16 days. Behavioural assessments (elevated plus maze, social interaction test, operant social reward) took place during the last six days of treatment. HC treatment reduced open-arm entries overall. For time on the open arms, there was an age-by-stress-by-treatment interaction: SS adolescent rats displayed more anxiety-like behaviour compared to SS adult rats in those treated with vehicle. For social interaction there was a stress-by-treatment interaction such that in controls, HC reduced interaction; in vehicle-treated rats, SS reduced interaction. Across ages, HC increased sensitivity to and motivation for social reward; adolescents showed higher overall social reward than adults. This study provides novel insights into the interaction of exogenous hormones and social stress on brain-behaviour relationships at different stages of development. • Ethinyl estradiol (EE) + levonorgestrel (LNG) produced an anxiogenic profile. • EE + LNG increased social reward sensitivity and motivation irrespective of age at treatment. • Social instability stress (SS) decreased social interaction. • Hormonal contraceptive and SS effects were mostly independent of age of treatment.
Lacasse et al. (Sat,) studied this question.