Repeated exposure to physiologically effective doses of contraceptive hormones ethinyl estradiol or levonorgestrel do not alter the reinforcing effects of a brief visual stimulus in ovary-intact rats

• Published in: Hormones and behavior 2024-05, Vol.161, p.105506, Article 105506
• Main Authors: McNealy, Kathleen R., Oevermann, Matthew W., Knabel, MacKenzie L., Fitzwater, Anna, Gipson, Cassandra D., Barrett, Scott T., Bevins, Rick A.
• Format: Article
• Language: English
• Subjects: Ethinyl estradiol; Hormonal contraceptives; Levonorgestrel; Operant; Rat; Sensory reinforcement; Sex hormones
• ISSN: 0018-506X; 1095-6867; 1095-6867
• DOI: 10.1016/j.yhbeh.2024.105506

Estradiol and progesterone potentiate and attenuate reward processes, respectively. Despite these well-characterized effects, there is minimal research on the effects of synthetic estrogens (e.g., ethinyl estradiol, or EE) and progestins (e.g., levonorgestrel, or LEVO) contained in clinically-utilized hormonal contraceptives. The present study characterized the separate effects of repeated exposure to EE or LEVO on responding maintained by a reinforcing visual stimulus. Forty ovary-intact female Sprague-Dawley rats received either sesame oil vehicle (n = 16), 0.18 μg/day EE (n = 16), or 0.6 μg/day LEVO (n = 8) subcutaneous injections 30-min before daily one-hour sessions. Rats' responding was maintained by a 30-sec visual stimulus on a Variable Ratio-3 schedule of reinforcement. The day after rats' last session, we determined rats estrous cycle phase via vaginal cytology before sacrifice and subsequently weighing each rat's uterus to further verify the contraceptive hormone manipulation. The visual stimulus functioned as a reinforcer, but neither EE nor LEVO enhanced visual stimulus maintained responding. Estrous cytology was consistent with normal cycling in vehicle rats and halting of normal cycling in EE and LEVO rats. EE increased uterine weights consistent with typical uterotrophic effects observed with estrogens, further confirming the physiological impacts of our EE and LEVO doses. In conclusion, a physiologically effective dose of neither EE nor LEVO did not alter the reinforcing efficacy of a visual stimulus reinforcer. Future research should characterize the effects of hormonal contraceptives on responding maintained by other reinforcer types to determine the generality of the present findings. •A brief visual stimulus functioned as a reinforcer.•Ethinyl estradiol and levonorgestrel did not alter visual stimulus reinforcement.•Estrous cycling was halted by low doses of ethinyl estradiol and levonorgestrel.•Ethinyl estradiol produced expected estrogen-evoked uterotrophy.