A rat model of oral hormonal contraception: Effects on drug preference and gonadal function

Gonadal hormones (e.g., estradiol and progesterone) influence response to, and preference for, drugs in females; however, how hormonal contraceptives, synthetic hormones that decrease gonadal hormone levels, affect drug preference is not known. The current experiment investigated whether oral administration of levonorgestrel (LNG), a synthetic progestin used in hormonal contraceptives, would lead to a reduction in amphetamine (AMPH) preference. Female rats were tested for their AMPH preference over 3 days (which also served as extinction sessions) after receiving oral administration of LNG (250 μg, 500 μg, or 2 mg) or during an estrous cycle stage associated with higher levels of gonadal hormones (i.e., proestrus/estrus). Our results show that AMPH preference was reduced for females on 500 μg and 2 mg of LNG across extinction sessions. Interestingly, only the 2 mg LNG dose led to a disruption in the naturally occurring estrous cycle. Uterine horn width, an index of estrogen exposure, was decreased in all LNG groups, but only the 500 μg and 2 mg LNG groups showed suppression of gonadal hormones, suggesting that both doses are sufficient for contraceptive use in rats. Our study demonstrates an effective and noninvasive oral LNG administration method in a rat model and further shows reduced AMPH preference by LNG. (PsycInfo Database Record (c) 2026 APA, all rights reserved).